High energy polyenergetic ion selection systems, ion beam therapy systems, and ion beam treatment centers

ABSTRACT

Devices and methods are provided for generating laser-accelerated high energy polyenergetic positive ion beams that are spatially separated and modulated based on energy level. The spatially separated and modulated high energy polyenergetic positive ion beams are used for radiation therapy. In addition, methods are provided for treating patients in radiation treatment centers using therapeutically suitable high energy polyenergetic positive ion beams that are provided by spatially separating and modulating positive ion beams. The production of radioisotopes using spatially separated and modulated laser-accelerated high energy polyenergetic positive ion beams is also provided.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application claims the benefit of U.S. provisional patentapplication Ser. No. 60/475,027, filed Jun. 2, 2003, the entirety ofwhich is incorporated by reference herein.

GOVERNMENT RIGHTS

The work leading to the disclosed invention was funded in whole or inpart with Federal funds from the National Institutes of Health and theHealth Resources and Services Administration. The Government may havecertain rights in the invention under NIH contract number CA78331 andHRSA Grant No. 4C76HF00691-01-01.

FIELD OF THE INVENTION

The present invention is related to the field of devices and methods forgenerating high energy ion beams. The present invention is also relatedto uses of high energy ion beams for radiation therapy. In addition, thepresent invention is related to the field of treating patients in cancertreatment centers using high energy ion beams.

BACKGROUND OF THE INVENTION

Radiation therapy is one of the most effective tools for cancertreatment. It is well known that the use of proton beams provides thepossibility of superior dose conformity to the treatment target as wellas providing a better normal tissue sparing, as a result of the Braggpeak effect, compared to photons (e.g., X-rays) and electrons. See, e.g.T. Bortfeld, “An analytical approximation of the Bragg curve fortherapeutic proton beams”, Med. Phys., 2024–2033 (1997). While photonsshow high entrance dose and slow attenuation with depth, protons have avery sharp peak of energy deposition as a function of beam penetration.As a consequence, it is possible for a larger portion of the incidentproton energy to be deposited within or very near the 3D tumor volume,thus avoiding radiation-induced injury to surrounding normal tissuesthat commonly occurs with x-rays and electrons.

Despite the dosimetric superiority characterized by the sharp protonBragg peak, utilization of proton therapy has lagged behind that ofphoton therapy. This lag is apparently due to the operating regime (thetotal operating cost for accelerator maintenance, energy consumption,and technical support) for proton accelerators being at least an orderof magnitude higher compared to electron/X-ray medical accelerators.Currently, proton therapy centers utilize cyclotrons and synchrotrons.See, e.g., Y. A. Jongen et al., “Proton therapy system for MGH's NPTC:equipment description and progress report”, Cyclotrons and theirApplications, J. C. Cornell (ed) (New Jersey: World Scientific) 606–609(1996); “Initial equipment commissioning of the North Proton TherapyCenter”, Proc. of the 1998 Cyclotron Conference (1998); and F. T. Cole,“Accelerator Considerations in the Design of a Proton Therapy Facility”,Particle Acceleration Corp. Rep (1991). Despite a somewhat limitednumber of clinical cases from these facilities, treatment records haveshown encouraging results particularly for well localizedradio-resistant lesions. See, e.g., M. Fuss et al., “Proton radiationtherapy (PRT) for pediatric optic pathway gliomas: Comparison with 3Dplanned conventional photons and a standard photon technique”, Int. J.Radiation Oncology Biol. Phys., 1117–1126 (1999); J. Slater et al.,“Conformal proton therapy for prostate carcinoma” Int. J. RadiationOncology Biol. Phys., 299–304 (1998); W. Shipley et al., “Advancedprostate cancer: the results of a randomized comparative trial of highdose irradiation boosting with conformal protons compared withconventional dose irradiation using photons alone”, Int. J. RadiationOncology Biol. Phys., 3–12 (1995); and R. N. Kjellberg, “StereotacticBragg Peak Proton Radiosurgery for Cerebral Arteriovenous Malformations”Ann Clin. Res., Supp. 47, 17–25 (1986). This situation could be greatlyimproved by the availability of a compact, flexible, and cost effectiveproton therapy system, which would enable the widespread use of thissuperior beam modality and therefore bring significant advances in themanagement of cancer.

Thus, there remains the problem of providing a practical solution for acompact, flexible and cost-effective proton therapy system. See, e.g.,C.-M. Ma et al., “Laser accelerated proton beams for radiation therapy”,Med. Phys., 1236 (2001); and E. Fourkal et al., “Particle in cellsimulation of laser-accelerated proton beams for radiation therapy”,Med. Phys., 2788–2798 (2002). Such a proton therapy system will requirethree technological developments: (1) laser-acceleration of high-energyprotons, (2) compact system design for ion selection and beamcollimation, and (3) the associated treatment optimization software toutilize laser-accelerated proton beams.

U.S. Patent Application Pub. No. US 2002/0090194 A1 (Tajima) discloses asystem and method of accelerating ions in an accelerator to optimize theenergy produced by a light source. It is disclosed that severalparameters may be controlled in constructing a target used in theaccelerator system to adjust performance of the accelerator system.

Simulations of the laser acceleration of protons reported by Fourkal etal., showed that, due to their broad energy spectrum, it is unlikelythat laser accelerated protons can be used for therapeutic treatmentswithout prior proton energy selection. If such an energy distribution isachieved, however, it should be possible to provide a homogeneous dosedistribution through the so-called Spread Out Bragg's Peak (“SOBP”).Using multiple beams (beamlets) it should also be possible to conformthe dose distribution to the target laterally (intensity modulation).Intensity-modulated radiation therapy (“IMRT”) using photon beams coulddeliver more conformal dose distribution to the target while minimizingthe dose to surrounding organs compared to conventional photontreatments. In “On the role of intensity-modulated radiation therapy inradiation oncology”, Med. Phys., 1473–1482 (2002), R. J. Shultz, et al.addressed the role of the intensity-modulated radiation therapy intreatments of specific disease sites. This topic of research is still inits latent stage requiring accumulation and analysis of more data, butthe findings of Shultz et al. suggest that at least there could be anadvantage of using IMRT for treatments of such sites as the digestivesystem (colorectal, esophagus, stomach), bladder and kidney.

Giving a homogeneous dose distribution in the target's depth directionmay be possible; see, e.g., C. Yeboah et al., “Intensity and energymodulated radiotherapy with proton beams: Variables affecting optimalprostate plan”, Med. Phys., 176–189 (2002); and A. Lomax, “Intensitymodulation methods for proton radiotherapy”, Phys. Med. Biol., 185–205(1999). Accordingly, Energy- and Intensity-Modulated Proton Therapy(“EIMPT”) should further improve target coverage and normal tissuesparing effects. In recent years, the planning and delivery of X-rayshas improved considerably so that the gap between the conventionalproton techniques and X-ray methods has decreased dramatically. The mainpathway of research has been toward the optimization of individualbeamlets and the calculation of optimal intensity distributions (foreach beamlet) for intensity modulated treatments. See, e.g., E. Pedroni,“Therapy planning system for the SIN-pion therapy facility”, inTreatment Planning for External Beam Therapy with Neutrons, ed. G.Burger, A. Breit and J. J. Broerse (Munich: Urban and Schwarzenberg);and T. Bortfeld et al., “Methods of image reconstruction fromprojections applied to conformation radiotherapy”, Phys. Med. Biol.,1423–1434 (1990). Unfortunately, the implementation of intensitymodulation for proton beams has lagged behind that of photons due to thedesign limitations of conventional beam delivery methods in protontherapy. See, e.g., M. Moyers “Proton Therapy”, The Modern Technology ofRadiation Oncology, ed. J. Van Dyk (Medical Physics Publishing, Madison,1999). Thus, there remains the problem of providing a combination of acompact proton selection and collimation device and treatmentoptimization algorithm to make EIMPT possible using laser-acceleratedproton beams.

Laser acceleration was first suggested in 1979 for electrons (T. Tajimaand J. M. Dawson, “Laser electron accelerator”, Phys. Rev. Lett.,267–270 (1979)), and rapid progress in laser-electron acceleration beganin the 1990's after Chirped Pulse Amplification (“CPA”) was invented (D.Strickland, G. Mourou, “Compression of amplified chirped opticalpulses,” Opt. Comm., 219–221 (1985)) and convenient high fluencesolid-state laser materials such as Ti:sapphire were discovered anddeveloped. The first experiment that has observed protons generated withenergy levels much beyond several MeV (58 MeV) is based on the PetawattLaser at Lawrence Livermore National Laboratory (“LLNL”). See, e.g., M.H. Key et al., “Studies of the Relativistic Electron Source and relatedPhenomena in Petawatt Laser Matter Interactions”, in First InternationalConference on Inertial Fusion Sciences and Applications (Bordeaux,France, 1999); and R. A. Snavely et al., “Intense high energy protonbeams from Petawatt Laser irradiation of solids”, Phys. Rev. Lett.,2945–2948 (2000). Until then, there had been several experiments thatobserved protons of energy levels up to 1 or 2 MeV. See, e.g., A.Maksimchuk et al., “Forward Ion acceleration in thin films driven by ahigh intensity laser”, Phys. Rev. Lett. 4108–4111, (2000). Anotherexperiment at the Rutherford-Appleton Laboratory in the U.K. has beenreported recently with proton energy levels of up to 30 MeV. See, e.g.,E. L. Clark et al., “Energetic heavy ion and proton generation fromultraintense laser-plasma interactions with solids”, Phys. Rev. Lett.,1654–1657 (2000).

It has long been understood that ion acceleration in laser-producedplasma relates to the hot electrons. See, e.g., S. J. Gitomer et al.,“Fast ions and hot electrons in the laser-plasma interaction”, Phys.Fluids, 2679–2686 (1986). A laser pulse interacting with the highdensity hydrogen-rich material (plastic) ionizes it and subsequentlyinteracts with the created plasma (collection of free electrons andions). The commonly recognized effect responsible for ion accelerationis a charge separation in the plasma due to high-energy electrons,driven by the laser inside the target (see, e.g., A. Maksimchuk et al.,Id., and W. Yu et al., “Electron Acceleration by a Short RelativisticLaser Pulse at the Front of Solid Targets”, Phys Rev. Lett.,570–573(2000)) or/and an inductive electric field as a result of theself-generated magnetic field (see, e.g., Y. Sentoku et al., “Bursts ofSuperreflected Laser Light from Inhomogeneous Plasmas due to theGeneration of Relativistic Solitary Waves”, Phys. Rev. Lett., 3434–3437(1999)), although a direct laser-ion interaction has been discussed forextremely high laser intensities, on the order of 10²² W/cm²; see, e.g.,S. V. Bulanov et al, “Generation of Collimated Beams of RelativisticIons in Laser-Plasma Interactions”, JETP Letters, 407–411 (2000). Theseelectrons can be accelerated up to multi-MeV energy levels (depending onlaser intensity) due to several processes, such as ponderomotiveacceleration by propagating laser pulse (W. Yu et al., Id.); resonantabsorption in which a part of laser energy goes into creation of aplasma wave which subsequently accelerates electrons (S. C. Wilks and W.L. Kruer, “Absorption of Ultrashort, ultra-intense laser light by solidsand overdense plasmas” IEEE J. Quantum Electron., 1954–1968 (1997)); and“vacuum heating” due to the v×B component of the Lorentz force (W. L.Kruer and K. Estabrook, “J×B heating by very intense laser light,” Phys.Fluids, 430–432 (1985)). Because of the number of mechanisms forelectron acceleration and the corresponding electric field generation,different regimes of ion acceleration are possible. Understanding themechanisms of ion acceleration in the interaction of laser pulse with asolid target and quantification of the ion yield in terms of thedependencies on the laser pulse and the plasma parameters are useful fordesigning laser proton therapy systems.

Having the quantified ion yield of a laser-accelerated proton ion beamalone is typically insufficient for preparing a therapeutically-suitableproton ion dose. Such proton ion beams have a wide energy distributionthat further require energy distribution shaping (i.e., the resultinghigh energy polyenergetic ion beam) to be therapeutically suitable. Inaddition to needing to shape the polyenergetic beam's energydistribution, beam size, direction and overall intensity need to becontrolled to provide proton beams that are therapeutically sufficientfor irradiating a target in a patient. Lower-energy protons typicallytreat shallower regions in a patient's body, whereas higher-energyprotons treat deeper regions. Thus, there remains the problem ofproviding systems and methods for forming therapeutically-suitablepolyenergetic ion beams from sources of laser-accelerated high energyprotons that are capable of treating a predetermined three dimensionalconformal region within a body. Such ion selection systems are presentlyneeded to provide low-cost, compact, ion therapy systems to enable thegreater availability of positive ion beam therapy to society.

SUMMARY OF THE INVENTION

The present inventor has now designed ion selection systems for formingtherapeutically-suitable polyenergetic ion beams. In a first aspect ofthe present invention there are provided ion selection systems, having acollimation device capable of collimating a laser-accelerated highenergy polyenergetic ion beam, the laser-accelerated high energypolyenergetic ion beam including a plurality of high energypolyenergetic positive ions; a first magnetic field source capable ofspatially separating the high energy polyenergetic positive ionsaccording to their energy levels; an aperture capable of modulating thespatially separated high energy polyenergetic positive ions; and asecond magnetic field source capable of recombining the modulated highenergy polyenergetic positive ions.

The present inventor has also designed methods of forming high energypolyenergetic positive ion beams from laser-accelerated high-energypolyenergetic ion beam sources that are suitable for ion beam therapy.Thus, in a second aspect of the present invention there are providedmethods of forming a high energy polyenergetic positive ion beam,including the steps of forming a laser-accelerated high energypolyenergetic ion beam including a plurality of high energypolyenergetic positive ions, the high energy polyenergetic positive ionscharacterized as having a distribution of energy levels; collimating thelaser-accelerated ion beam using a collimation device; spatiallyseparating the high energy positive ions according to their energylevels using a first magnetic field; modulating the spatially separatedhigh energy positive ions using an aperture; and recombining themodulated high energy polyenergetic positive ions using a secondmagnetic field.

Within additional aspects of the invention there are providedlaser-accelerated high energy polyenergetic positive ion therapy systemsthat are capable of delivering therapeutic polyenergetic beams to athree-dimensional conformal target in a body. In these aspects of theinvention there are provided laser-accelerated high energy polyenergeticpositive ion therapy systems, including: a laser-targeting system, thelaser-targeting system having a laser and a targeting system capable ofproducing a high energy polyenergetic ion beam, the high energypolyenergetic ion beam including high energy positive ions having energylevels of at least about 50 MeV; an ion selection system capable ofproducing a therapeutically suitable high energy polyenergetic positiveion beam from a portion of the high energy positive ions; and an ionbeam monitoring and control system.

In another aspect of the invention, there are provided methods oftreating patients with a laser-accelerated high energy polyenergeticpositive ion therapy system, including the steps of identifying theposition of a targeted region in a patient; determining the treatmentstrategy of the targeted region, the treatment strategy includingdetermining the dose distributions of a plurality of therapeuticallysuitable high energy polyenergetic positive ion beams for irradiatingthe targeted region; forming the plurality of therapeutically suitablehigh energy polyenergetic positive ion beams from a plurality of highenergy polyenergetic positive ions, the high energy polyenergeticpositive ions being spatially separated based on energy level; anddelivering the plurality of therapeutically suitable high energypolyenergetic positive ion beams to the targeted region according to thetreatment strategy.

In a related aspect of the invention, there are providedlaser-accelerated ion beam treatment centers, including: a location forsecuring a patient; a laser-accelerated high energy polyenergeticpositive ion therapy system capable of delivering a therapeuticallysuitable polyenergetic positive ion beam to a patient at the location,the ion therapy system having a laser-targeting system, thelaser-targeting system having a laser and at least one target assemblycapable of producing a high energy polyenergetic ion beam, the highenergy polyenergetic ion beam including high energy polyenergeticpositive ions having energy levels of at least about 50 MeV; an ionselection system capable of producing a therapeutically suitable highenergy polyenergetic positive ion beam using the high energypolyenergetic positive ions, the high energy polyenergetic positive ionsbeing spatially separated based on energy level; and a monitoring andcontrol system for the therapeutically suitable high energypolyenergetic positive ion beam.

In additional aspects of the present invention there are providedmethods of producing radioisotopes using the laser-accelerated highenergy polyenergetic ion beams provided herein. In these aspects of thepresent invention there are provided methods of producing radioisotopes,including the steps of forming a high energy polyenergetic positive ionbeam, including forming a laser-accelerated ion beam having a pluralityof high energy positive ions, the high energy polyenergetic positiveions characterized as having an energy distribution; collimating thelaser-accelerated high energy polyenergetic ion beam using at least onecollimation device; spatially separating the high energy polyenergeticpositive ions according to energy using a first magnetic field;modulating the spatially separated high energy polyenergetic positiveions using an aperture; recombining the spatially separated high energypolyenergetic positive ions using a second magnetic field; andirradiating a radioisotope precursor with the recombined spatiallyseparated high energy polyenergetic positive ions.

Other aspects of the present invention will be apparent to those skilledin the art in view of the detailed description of the invention asprovided herein.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing summary, as well as the following detailed description, isfurther understood when read in conjunction with the appended drawings.For the purpose of illustrating the invention, there is shown in thedrawings exemplary embodiments of the invention; however, the inventionis not limited to the specific methods and instrumentalities disclosed.In the drawings:

FIG. 1 is a schematic diagram of one embodiment of the polyenergetic ionselection system of the present invention. E represents the electricfield of the pulse polarized along the y-axis. k is the wave vector ofthe pulse directed along the x-axis. The pulse is initialized to theleft of the target and propagates from the left to the right side of thediagram.

FIG. 2( a) shows the energy distribution of protons at t=400/ω_(pe).ω_(pe)=1.18*10¹⁵ rad/s. N represents the number of protons in a givenenergy range when the total number of protons used in the simulation is1048576.

FIG. 2( b) shows the angular distributions of accelerated protons att=400/ω_(pe). The solid line shows the distribution for protons in theenergy range 95≦E≦105 MeV, the dotted line represents the protons in theenergy range 145≦E≦155 MeV, and the dashed line represent protons in theenergy range 245≦E≦255 MeV. The laser pulse length and intensity are 14fs and I=1.9*10²² W/cm² correspondingly. The error bars representone-standard deviation statistical uncertainty.

FIG. 3 shows the proton spatial distributions N=N(y) per laser pulse fora given number of the total protons simulated versus y-axis at the planex=40 cm, z=0 cm, for a primary collimator opening of 1×1 cm² defined at100 cm source to surface distance (“SSD”). N represents the number ofprotons in a given range of spatial y-coordinate. The solid linerepresents protons in the energy range 80≦E≦90 MeV, the dotted linerepresents protons in the energy range 110≦E≦120 MeV, the dashed linerepresents protons in the energy range 140≦E≦150 MeV, the dashed-dottedline represents protons in the energy range 190≦E≦200 MeV and thedashed-two dotted line represents protons in the energy range 250≦E≦260MeV.

FIG. 4 shows the proton energy distributions N=N(E) per laser pulse fora given number of the total protons simulated versus energy at planex=40 cm, z=0 cm, for a primary collimator opening of 1×1 cm² defined at100 cm SSD. The solid line represents protons with energy distributionpeaked at E=81 MeV, the dotted line represents protons with energydistribution peaked at E=114 MeV, the dashed line represents protonswith energy distribution peaked at E=145 MeV, the dashed-dotted linerepresents protons with energy distribution peaked at E=190 MeV and thedashed-two dotted line represents protons with energy distributionpeaked at E=250 MeV.

FIG. 5 shows the depth dose distributions for protons with energyspectra shown in FIG. 4 normalized to the initial proton fluence. Thesolid line represents the dose distribution calculated using the protonspectrum peaked at E=81 MeV, the dotted line represents the dosedistribution calculated using the proton spectrum peaked at E=114 MeV,the dashed line represents the dose distribution calculated using theproton spectrum peaked at E=145 MeV, the dashed-dotted line representsthe dose distribution calculated using the proton spectrum peaked atE=190 MeV, and the dashed-two dotted line represents the dosedistribution calculated using the proton spectrum peaked at E=240 MeV.The primary collimator opening is 1×1 cm² defined at 100 cm SSD.One-standard deviation associated with the calculations is on the orderof 1%.

FIG. 6( a) shows the proton spatial distributions N=N(y) versus y-axisat the plane x=40 cm, z=0 cm, for a primary collimator opening of 5×5cm² defined at 100 cm SSD. The solid line represents protons in theenergy range 80≦E≦90 MeV, the dotted line represents protons in theenergy range 110≦E≦120 MeV, the dashed line represents protons in theenergy range 140≦E≦150 MeV, the dashed-dotted line represents protons inthe energy range 180≦E≦190 MeV and the dashed-two dotted line representsprotons in the energy range 245≦E≦255 MeV.

FIG. 6( b) shows the proton energy distributions N=N(E) versus energy atplane x=40 cm, z=0 cm, for a primary collimator opening of 5×5 cm²defined at 100 cm SSD. The solid line represents protons with energydistribution peaked at E=76 MeV, the dotted line represents protons withenergy distribution peaked at E=95 MeV, the dashed line representsprotons with energy distribution peaked at E=133 MeV, the dashed-dottedline represents protons with energy distribution peaked at E=190 MeV andthe dashed-two dotted line represents protons with energy distributionpeaked at E=208 MeV.

FIG. 7 shows the energy spread versus the primary collimator opening.The solid line corresponds to the protons peaked at energy 103 MeV, thedashed line corresponds to the protons peaked at energy 124 MeV anddashed-dotted line corresponds to the protons peaked at energy 166 MeV.

FIG. 8 shows the depth dose distributions for protons with energyspectra shown in FIG. 6( b) normalized to the initial proton fluence.The solid line represents the dose distribution calculated using theproton spectrum peaked at E=76 MeV, the dotted line represents the dosedistribution calculated using the proton spectrum peaked at E=133 MeV,the dashed line represents the dose distribution calculated using theproton spectrum peaked at E=190 MeV, the dashed-dotted line representsthe dose distribution calculated using the proton spectrum peaked atE=208 MeV. The primary collimator opening is 5×5 cm² defined at 100 cmSSD. One-standard deviation associated with the calculations is on theorder of 1%.

FIG. 9( a) shows the modulated proton energy distribution based on 1×1cm² primary collimator opening defined at 100 cm SSD. η represents thenumber of protons in a given energy range normalized to the number ofprotons with energy E=152 MeV. The solid line represents the energyspectrum calculated using polyenergetic proton beams. The dashed linerepresents the energy spectrum calculated using mono-energetic protons.

FIG. 9( b) shows the SOBP dose distribution with a 4×4 cm² fieldnormalized to the initial fluence of protons. The solid line representsthe dose distribution calculated using 16 1×1 cm² beamlets with thespectrum shown in FIG. 9( a) (solid line). The dashed line representsthe dose distribution calculated using a spectrum of idealmono-energetic protons. One-standard deviation associated with thecalculations is on the order of 1%.

FIG. 10 shows the temporal evolution of the proton cloud's size. Thesolid line represents the numerical solution to Equation 7. The pointsrepresent the results of PIC simulations. τ represents time in units ofion plasma frequency, τ=ω_(pi)t.

FIG. 11 shows dose distributions of various radiation modalities as afunction of depth in water.

FIG. 12 shows the JanUSP laser system and target chambers.

FIG. 13 shows the angular distribution of laser-accelerated protons,relative number per radian (top) and maximum proton energy as a functionof laser pulse length (bottom) for a laser intensity of 10²¹ W/cm².

FIG. 14 shows Laser-accelerated proton energy spectra collimated by asmall aperture (top) and dose distributions from these spectra (bottom)for a laser intensity of 10²¹ W/cm² and 50 fs pulse length.

FIG. 15 shows depth dose curves of protons of different energy levelsand intensities to form a SOBP (top) using monoenergies (solid) or thespectra in FIG. 14 (dashed), and the weight of each energy spectrum forthe spectrum-based SOBP (bottom).

FIG. 16 shows isodose distributions for a 8-field EIMPT plan (a) and a8-field photon IMRT plan (b), and DVHs for the target (c) and the rectum(d) for the same patient geometry using 4 different treatmentmodalities. The prescribed target (PTV) dose is 50 Gy. The isodose linesrepresent 5, 15, 25, 35, 40, 45, 50 and 55 Gy.

FIG. 17 shows a schematic diagram of one embodiment of alaser-accelerated positive ion beam treatment center (e.g., laser-protontherapy unit, the laser is not shown) having a laser beam line and beamscanning mechanism of the laser-driven proton therapy system of theinvention.

FIG. 18 shows a schematic of one embodiment of the ion selection systemof the present invention showing tracks calculated for 50, 150 and 250MeV protons in 3 T magnetic fields (moving from left to right). Protonshaving energy levels within an energy range pass by the beam stoppersand recombine through an exit collimator and the primary monitor chamber(PMC). The high-energy proton stopper also serves as a photon stopperand the electrons are deflected downward and terminated by the electronstopper. The secondary monitor chamber (SMC) measures both the energyspread and intensity change.

FIG. 19 shows (a) angular distributions of protons in a raw beam (eachcurve represents one energy); (b) spatial spread of protons after goingthrough magnet fields (each circle represents one energy) and arectangular aperture to select desired energy levels; (c) Energyspectrum of raw protons (solid) and selected protons (dashed); and (d)Depth dose curve of raw protons (solid) and selected protons (dashed).

FIG. 20 depicts (a) angular distributions for different energy protonsin the raw laser-proton beam; (b) spatial spreads of protons ofdifferent energy levels after going through a square collimator and themagnets. A square aperture on the right hand side of (b) is used toselect a desired energy.

FIG. 21 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 22 depicts a perspective view of an embodiment of an ion selectionsystem of the present invention.

FIG. 23 depicts a sectional view of an ion selection system depicted inFIG. 22.

FIG. 24 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 25 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 26 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 27 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 28 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 29 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 30 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 31( a) depicts a sectional view of an embodiment of an ionselection system of the present invention.

FIG. 31( b) depicts a schematic illustration of a collimator 2 (i.e., amultileaf collimator) in the x–z plane showing openings in thecollimator for selecting positive ions of a particular energy.

FIG. 32 depicts a schematic illustration of an energy selectionaperture.

FIG. 33 depicts a schematic illustration of a multileaf collimator inthe x–z plane: (a) shows openings in the multileaf collimator forselecting low energy ions; (b) shows openings in the multileafcollimator for selecting high energy ions.

FIG. 34 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 35 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 36 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 37 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 38 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 39 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 40 depicts a sectional view of an embodiment of an ion selectionsystem of the present invention.

FIG. 41 depicts a sectional view of a laser-accelerated high energypolyenergetic positive ion therapy system of the present invention.

FIG. 42( a) depicts a perspective view of an embodiment of alaser-accelerated high energy polyenergetic positive ion beam treatmentcenter.

FIG. 42( b) depicts a perspective view of an embodiment of alaser-accelerated high energy polyenergetic positive ion beam treatmentcenter that includes an optical monitoring and control system.

FIG. 42( c) depicts a perspective view of an embodiment of alaser-accelerated high energy polyenergetic positive ion beam treatmentcenter that includes more than one ion therapy system.

FIG. 42( d) depicts a perspective view of an embodiment of alaser-accelerated high energy polyenergetic positive ion beam treatmentcenter that includes more than one ion therapy system, with each of theion therapy systems having an optical monitoring and control system.

FIG. 43 depicts a flow chart of an embodiment of a method of treating apatient using polyenergetic high energy positive ions.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The following abbreviations and acronyms are used herein:

CORVUS a treatment optimization system for photon IMRT from NOMOS

CPA chirped pulse amplification

CT computer-aided tomography

DICOM Digital Imaging and Communications in Medicine

DICOM RT DICOM Radiation Therapy Supplement

DVH dose-volume histogram

EIMPT energy- and intensity-modulated proton therapy

EGS4 Electron Gamma Shower (version 4) Monte Carlo code system

GEANT(3) a Monte Carlo system for radiation (proton, neutron, etc)simulation

IMRT intensity-modulated (photon) radiation therapy

JanUSP a high power (10¹⁹–10²¹ W/cm²) laser at LLNL

LLNL Lawrence Livermore National Laboratory

LLUMC Loma Linda University Medical Center, Loma Linda, Calif.

MCDOSE an EGS4 user-code for dose calculation in a 3-D geometry

MGH Massachusetts General Hospital, Boston, Mass.

MLC multileaf collimator

NOMOS NOMOS Corp., Sewickley, Pa.

NTCP normal tissue complication probability

PC personal computer

PIC particle-in-cell (simulation technique for laser plasma physics)

PMC primary monitor chamber

PSA prostate-specific antigen

PTV planning target volume

PTRAN a Monte Carlo code system for proton transport simulation

RTP radiotherapy treatment planning

SMC secondary monitor chamber

SOBP spread out Bragg peak (for proton/ion beams)

SSD source-surface distance

TCP tumor control probability

MeV million electron volts

GeV billion electron volts

T Tesla

As used herein, the term “protons” refers to the atomic nuclei ofhydrogen (H¹) having a charge of +1.

As used herein, the term “positive ions” refers to atoms and atomicnuclei having a net positive charge.

As used herein, the term “polyenergetic” refers to a state of matterbeing characterized as having more than one energy level.

As used herein, the term “high energy” refers to a state of matter beingcharacterized as having an energy level greater than 1 MeV.

As used herein, the term “beamlet” refers to a portion of a high energypolyenergetic positive ion beam that is spatially separated, orenergetically separated, or both spatially and energetically separated.

The terms “primary collimator”, “primary collimation device”, “initialcollimator”, and “initial collimation device” are used interchangeablyherein.

The terms “energy modulation system” and “aperture” are usedinterchangeably when it is apparent that the aperture referred to iscapable of modulating a spatially separated high energy polyenergeticpositive ion beam.

All ranges disclosed herein are inclusive and combinable.

In one embodiment of the present invention there is provided alaser-accelerated polyenergetic ion selection system for radiationtherapy. The design of this system typically includes a magnetic fieldsource that is provided to spatially separate protons of differentenergy levels. A magnetic field source is also provided to separate outplasma electrons that initially travel with the protons. While these twomagnetic field sources are typically provided by the same magnetic fieldsource, two or more separate magnetic field sources may be provided tocarry out these functions. After the protons have been spatiallyseparated, one or more apertures are typically provided to select anenergy distribution needed to cover the treatment target in the depthdirection for a given beamlet. The form of an aperture is dictated bythe location as well as the depth dimension of the target, as describedmore fully below. Once the spatial position and the target size areknown, the proton energy spectrum needed to cover the target for a givenbeamlet in the depth direction is calculated by combining the depth dosecurves of different proton energy levels, as described more fully below.Due to the angular distribution of protons, a primary collimation deviceis typically employed to reduce spatial mixing of different energyprotons. The primary collimation device is typically employed tocollimate the positive ions into a magnetic field that separates theions by energy levels. As a result of this spatial mixing, the protonenergy spectrum in a given spatial location typically has a small spreadthat depends on the energy of the protons. The depth dose curves aretypically calculated using the spread out (i.e., polyenergetic) protonspectrum. In this regard, the depth dose curves for the proton energymodulation are typically modified to account for this polyenergeticspreading effect, as described more fully below.

Description of a proton selection and collimation system: In oneembodiment of the present invention there is provided an ion selectionand collimation device needed for proton energy modulation. Using the 2Dparticle in cell simulation code (PIC), described by C. K. Birdsall andA. B. Langdon in Plasma Physics via Computer Simulation (McGraw-HillBook Company, Singapore 1985), the interaction of a petawatt laser pulsewith a thin dense foil (hydrogen rich) was simulated, yielding protonswith energy well beyond 200 MeV and maximum energy reaching 440 MeV. Thesimulations were performed for a 3.6 μm (in the radial direction) fullwidth at half-maximum (FWHM, 14 femtosecond (fs) linearly polarizedlaser pulse with a wavelength, λ=0.8 μm and intensity I=1.9×10²² W/cm²,normally incident onto a thin dense plasma slab (ionized foil) with adensity thirty times higher than the critical densityn_(cr)=4π²m_(e)c²ε₀/(e²λ²) and thickness d≈1 μm. Such la reach of therecent technological developments, as described by G. A. Mourou et al.,in “Ultrahigh-Intensity Lasers: Physics of the Extreme on a Tabletop”,Physics Today, 22–28 (1998). The basic configuration of such as laserlight source system is described in U.S. Pat. No. 5,235,606, issued Aug.10, 1993 to Mourou et al., which is incorporated by reference herein.U.S. patent application Ser. No. 09/757,150 filed by Tajima on Jan. 8,2001, Pub. No. U.S. 2002/0090194 A1, Pub. Date Jul. 11, 2002, “LaserDriven Ion Accelerator” discloses a system and method of acceleratingions in an accelerator using such a laser light source system, thedetails of which are incorporated by reference herein in their entirety.

The protons coming from a thin foil are typically accelerated in theforward direction by the electrostatic field of charge separationinduced by the high intensity laser. Further details of this process aredescribed by V. Yu. Bychenkov et al., in “High energy ion generation ininteraction of short laser pulse with solid density plasma”, Appl. Phys.B, 207–215 (2002). Over a period of several tens of plasma frequencyω_(p)=√{square root over (ne²/m_(e)ε₀)} cycles, protons are typicallyaccelerated to relativistic energy levels. The maximum value of theproton energy levels typically depend on several factors, includinglaser pulse length and intensity, and plasma foil thickness. The latetime dynamics can be discerned by PIC code, which shows that protonsreach a stationary distribution (energy, angular) and move in aformation together with the electrons. This reassures the preservationof the low proton emittance, shielding proton space charge, whichotherwise could be detrimental to the emittance. The angulardistribution of protons exhibits the spread which depends on the energy.Typically, the general trend is such that the higher the energy of theaccelerated protons, the more they are emitted in the forward direction.The depth dose distribution calculated using the laser-acceleratedproton spectrum shows that the polyenergetic positive ion spectrumemitted from the target typically cannot be readily used for radiationtreatments. A high energy deposition to the area beyond the effectiveBragg peak typically arises from the high entrance dose to thesuperficial structures and the long tails in the polyenergetic dosedistributions. Thus, in one embodiment of the present invention, onedelivers a homogeneous dose to the tumor volume to minimize the dose tothe surrounding healthy tissues. This is achieved by providing an ion(e.g., proton) selection and collimation device that generates thedesired polyenergetic proton energy distribution. This device separatespolyenergetic positive ions (e.g., protons) into spatial regionsaccording to their energy. The spatially separated regions of thepositive ions are subsequently controlled using at least one magneticfield. The spatially separated positive ions are controllably modulatedusing an aperture to provide the desired dose. Optionally, the devicealso includes a magnetic field source for generating a magnetic field toeliminate the plasma electrons that travel with the positive ions. Thisoptional magnetic field source can be the same or a different magneticfield as the one spatially separating the polyenergetic positive ions.This magnetic field is also useful for eliminating plasma electronstraveling together with the laser-accelerated positive ions.

A schematic diagram of one embodiment of the ion selection system (100)is provided in FIG. 1. Referring to this figure, there is provided aseries of magnetic field sources that produce a magnetic field patternB=B(z)e_(z), the z-direction being perpendicular to the page. A firstmagnetic field source provides a first magnetic field (102), listed as“5.0 T into page”, at a distance from 5 cm to 20 cm from a plasma target(104) located at 0 cm along the x (primary beam) axis (114). High energypolyenergetic positive ions (110) are generated by the interactionbetween the plasma target (104) with a suitable laser pulse (not shown).A beam of high energy polyenergetic positive ions (e.g., protons) (106)enter the first magnetic field (102) after exiting an initialcollimation device (108). The protons are shown exiting the initialcollimation device (108) into the first magnetic field (102), theprotons being characterized as having an angular spread. A secondmagnetic field (112) source provides a second magnetic field listed as“5.0 T into page” at a distance from 60 cm to 75 cm from the plasmatarget (104) along the x (primary beam) axis (114). High energypolyenergetic positive ions (116) (protons in certain embodiments) enterthe second magnetic field (112) after exiting an aperture (118). Alsoshown in FIG. 1 is a third magnetic field source providing a thirdmagnetic field (120), which is listed as “5.0 T out of page” at adistance from 25 cm to 55 cm from the plasma target (104) located at 0cm along the x axis (114). The x axis as drawn is parallel to the beamaxis (114) of the laser in this embodiment. Other coordinateorientations and coordinate systems, such as cylindrical and sphericalcoordinate systems, can be suitably used. High energy polyenergeticpositive ions (126) enter the third magnetic field (120) after exitingthe first magnetic field (102). The first magnetic field (102) is shownspatially separating the trajectories (128) of the high energypolyenergetic positive ions by energy level. The third magnetic field(120) is shown bending the trajectories of spatially separated ions(130) towards the aperture (118). The aperture modulates the ion beam bycontrollably selecting a portion of the spatially separated ions, asdescribed further herein. The third magnetic field (120) is also shownbending the trajectories of the spatially separated polyenergeticpositive ions (132) towards the beam axis and towards the secondmagnetic field (112). The second magnetic field (112) recombines thespatially separated and modulated ions (134) to form a recombined ionbeam (136). The recombined ion beam (136) is shown entering a secondarycollimation device (138). Upon exiting the secondary collimation device(138), a high energy polyenergetic positive ion beam is provided that issuitable for use in high energy polyenergetic positive ion radiationtherapy. Suitable magnetic field sources for this and variousembodiments of the present invention typically have a magnetic fieldstrength in the range of from about 0.1 to about 30 Tesla, and moretypically in the range of from about 0.5 to about 5 Tesla. The Lorentzforce of the magnetic field typically spreads out the polyenergeticprotons. The lower energy protons (140) typically are deflected morefrom their original trajectories exiting the initial collimation device108) (“initial collimator”) than are the high energy protons (142).

As described herein, many of the embodiments of the present inventionuse magnetic field sources to provide magnetic fields for manipulatingthe positive ion beams. In additional embodiments of the presentinvention one or more of the magnetic field sources are replaced by, orcombined with, one or more electrostatic field sources for manipulatingthe positive ion beams.

The initial collimator (108) typically defines the angular spread of theincoming beam (106) entering the first magnetic field (102). The tangentof the angle of the beam spread of the beam (106) exiting the initialcollimator (108) is typically about the ratio of one half the distanceof the initial collimator exit opening (144) where the beam exits thecollimator to the distance of the collimator exit opening (144) to theproton beam source (i.e., the plasma target, 104). Typically, this angleis less than about 1 radian. The emitting angle is the angle of theinitial energy distribution exiting the target system (i.e., target, 104and initial collimation device, 108). Electrons (146) are typicallydeflected in the opposite direction from the positive ions by the firstmagnetic field and absorbed by a suitable electron beam stopper (148).Suitable electron stoppers (148) include tungsten, lead, copper or anymaterial of sufficient thickness to attenuate the electrons and anyparticles they generate to a desired level. The aperture (118) istypically used to select the desired energy components, and the matchingmagnetic field setup (in this embodiment, the second magnetic field,112) is selected that is capable of recombining the selected protons(134) into a polyenergetic positive ion beam. Suitable aperturestypically can be made from tungsten, copper or any other materials ofsufficient thickness that are capable of reducing the energy levels ofpositive ions. This energy level reduction is typically carried out tosuch a degree that the positive ions can be differentiated from thoseions that do not go through the aperture. In various embodiments of thepresent invention, the aperture geometry can be a circular, rectangular,or irregular-shaped opening (150)(or openings) on a plate (152)(orslab), which when placed in a spatially separated polyenergetic ionbeam, is capable of fluidically communicating a portion of the ion beamtherethrough. In other embodiments, the aperture (118) can be made froma plate that has multiple openings that are controllably selected, suchas by physical translation or rotation into the separated ion beam tospatially select the desirable energy level or energy levels to modulatethe separated ion beam. The modulation of the ion beam gives rise to atherapeutically suitable high energy polyenergetic positive ion beam(136) as described herein. Suitable apertures include multi-leafcollimators. In addition to controllably selecting the spatial positionof the openings that fluidically communicate the spatially separated ionbeams, the aperture openings may also be controllably shaped or multiplyshaped, using regular or irregular shapes. Various combinations ofopenings in the aperture (118) are thus used to modulate the spatiallyseparated ion beam (130). The spatially separated positive ions (132)are subsequently recombined using the second magnetic field (134).

The high and low energy positive ion (e.g., proton beam) stoppers (154and 156, respectively) typically eliminate unwanted low-energy particles(140) and high-energy particles (not shown). Because of the broadangular distribution of the accelerated protons (which depends on agiven energy range), there is typically a spatial mixing of differentenergy positive ions after they pass through the first magnetic field.For example, a portion of the low energy protons may go to regions wherethe high energy particles reside, and vice versa. Reducing the spatialmixing of protons is typically carried out by introducing a primarycollimation device, such as the initial collimation device 108 of theembodiment depicted in FIG. 1. A primary collimation device is typicallyused to collimate protons to the desired angular distribution.

As described further below, proton spatial differentiation is typicallycarried out by passing the positive ions through a small collimatoropening prior to their entering the first magnetic field. An example ofa small collimator opening is depicted in FIG. 1 as the initialcollimator opening (144). Typically, the collimator exit opening (144)is not arbitrarily small, since smaller openings typically lower thedose rate and increase the treatment time. As a result of the finitesize of the collimator opening (144), the protons are typicallyspatially mixed. Accordingly, any given spatial location for acollimator opening (however small) typically provides a polyenergeticproton energy distribution. While not being bound by any particulartheory of operation, the energy modulation calculations take intoaccount the polyenergetic characteristics of the positive ions enteringthe ion selection device to provide the needed depth dose curves. Thepolyenergetic characteristics of these positive ions is understoodthrough the influence of the magnetic field on the dynamics of thepositive ions. The following description is directed to the dynamics ofprotons, as one illustrative embodiment. Additional embodiments to otherpositive ions in addition to protons are also envisioned.

To describe the proton's dynamics in the magnetic field, a numericalcode is written which solves the following equation of motion,

$\begin{matrix}{\frac{\mathbb{d}p_{i}}{\mathbb{d}t} = {e\; v_{i} \times B}} & (1)\end{matrix}$where p=m_(p)v/√{square root over (1−v²/c²)}, B is the magneticinduction vector, m_(p) is the proton rest mass and i signifies theparticle number. For one embodiment of the present invention, thisequation was solved using a symplectic integration algorithm developedby J. Candy and W. Rozmus in “A Symplectic Integration Algorithm forSeparable Hamiltonian Functions “, J. Comp. Phys. 230–239 (1991). Theinitial conditions [(r₀ ^(i), v₀ ^(i))] were obtained from the PICsimulation data, which provided the phase-space distribution forprotons. The contribution of the self-consistent fields on the protondynamics were neglected, since the Lorentz force created by the externalmagnetic field to separate the electrons from the protons is greater forthe magnetic field induction used in the calculations than the Coulombforce in the region beyond the initial collimation device. Using theequation of balance between the Lorentz and the inter-particle Coulombforces, one arrives at a condition for particles spatial separationdistance for which the magnetic force prevails over the Coulomb force,

$\begin{matrix}{r > \left( \frac{e}{4\;\pi\; ɛ_{0}{Bv}} \right)^{1/2}} & (2)\end{matrix}$where B is the magnitude of the magnetic field, v is the particlevelocity and e is an elementary charge. The average inter-particledistance r can be obtained from the particle density r=n^(−1/3), thusthe inequality (2) can be rewritten in the form:

$\begin{matrix}{n < \left( \frac{4\;\pi\; ɛ_{0}{Bv}}{e} \right)^{3/2}} & (3)\end{matrix}$

Providing the lowest therapeutic energy protons of about 50 MeV, whichcorresponds to proton velocity of v=0.3c, and the magnetic fieldinduction B=5 T, the condition (3) gives, n<2*10²⁰ cm⁻³. The particledensity in the region beyond the initial collimation device can beestimated using the arguments presented by E. Fourkal et al. in“Particle in cell simulation of laser-accelerated proton beams forradiation therapy”, Id. (2002). In this region the particle density isn=4*10¹³ cm⁻³, which is far below the estimated threshold value of2*10²⁰ cm⁻³. This estimate validates the assumption of the insignificantcontribution of the self-consistent electrostatic field on the protondynamics in the external magnetic field.

The calculations of the proton dynamics in the magnetic field have alsoneglected such boundary effects as edge focusing due to the influence ofthe fringing field patterns at the edge of a sector field. These effectsare expected to be small in the bulk of the selection system due to thecanceling action of alternating magnetic field patterns (with the sameabsolute value of the field induction). As the positive ions (e.g.,protons) leave the final field section, the boundary fringe field canintroduce some focusing effect. This effect can be accounted for byusing the magnetic field distribution at the boundary.

Monte Carlo calculations: While not being bound by any particular theoryof operation, the GEANT3 Monte Carlo radiation transport code is usedfor dose calculations. GEANT3 is used to simulate the transport andinteractions of different radiation particles in different geometries.The code can run on different platforms. A detailed description of theoperation and usage of GEANT3 has been given by R. Brun et al., inGEANT3—Detector description and simulation tool Reference Manual (1994).GEANT3 is equipped with different user selectable particle transportmodes. Being more versatile than most Monte Carlo codes concerning theproduction of secondaries, GEANT3 has three options to deal with theserays. An important user controlled variable for these options is DCUTEbelow which the secondary particle energy losses are simulated ascontinuous energy loss by the incident particle, and above it they areexplicitly generated. In the first option, the secondary particles areproduced over the entire energy range of the incident particle. Thismode is termed as “no fluctuations”. The second mode of energy loss is“full fluctuations”, in which secondaries are not generated, and theenergy loss straggling is sampled from a Landau (“On the energy loss offast particles by ionization”, J. Phys. USSR, 201–210 (1944)), Vavilov(“Ionisation losses of high energy heavy particles”, Soviet PhysicsJETP, 749–758 (1957)) or Gaussian distribution each according to itsvalidity limits (R. Brun et al., Id.). The third is “restrictedfluctuations”, with generation of secondaries above DCUTE and restrictedLandau fluctuations below DCUTE. In principle, choosing energy lossfluctuations typically carries an advantage if energy deposited isscored in voxel sizes larger than the range of secondaries. This resultsin great savings of computation time and avoids tracking a large numberof secondaries generated below DCUTE. Typically, a continuous energyloss by the incident particle is assumed according to the Berger-Seltzerformulae.

Moliere multiple scattering theory is used by default in GEANT3.Multiple scattering is well described by Moliere theory. See, e.g., G.Z. Moliere, “Theorie der Streuung schneller geladener Teilchen I:Einzelstreuung am abgeschirmten Coulomb-Feld”, Z. Naturforsch., a,133–145 (1947); and G. Z. Moliere, “Theorie der Streuung schnellergeladener Teilchen II: Mehrfach-und Vielfachstreuung”, Z. Naturforsch.,a, 78–85 (1948). A limiting factor in the Moliere theory is the averagenumber of Coulomb scatters Ω₀ for a charged particle in a step. WhenΩ₀<20, the Moliere theory is typically not applicable. According to E.Keil et al. in “Zur Eifach-und Mehrfachstreuung geladener Teilchen”, Z.Naturforsch, a, 1031–1048 (1960), the range 1<Ω₀≦20 is called the pluralscattering regime. In this range a direct simulation method is used forthe scattering angle in GEANT3 (R. Brun et al., Id.). A simplificationof the Moliere theory by a Gaussian form is also implemented in GEANT3.The Gaussian multiple scattering represents Moliere scattering to betterthan 2% for 10<Ω₀≦10⁸.

The hadronic interactions in matter (elastic, inelastic, nuclearfission, neutron nuclear capture) are described by two softwareroutines, GHEISHA and FLUKA, which are available to users of GEANT. TheGHEISHA code generates hadronic interactions with the nuclei of thecurrent tracking medium, evaluating cross-sections and sampling thefinal state kinematics and multiplicity, while the GEANT philosophy ispreserved for the tracking purposes. A number of routines that exist inGHEISHA are responsible for generating the total cross-sections forhadronic interactions, calculating the distance to the next hadronicinteraction according to the total cross-sections and finally the mainsteering routine for the type of occurred hadronic interaction. FLUKA isa simulation program, which as a standalone code contains transport andthe physical processes for hadrons and leptons and tools for geometricaldescription. In GEANT, only the hadronic interaction part is included.As with the GHEISHA package, the FLUKA routines can compute the totalcross-sections for hadronic processes, and perform the sampling betweenelastic and inelastic processes. The cross-sections for both types ofinteractions are computed at the same time as the total cross-section.Subsequently, a particle is sent to the elastic or inelastic interactionroutines. After the interaction, the eventual secondary particles arewritten to the GEANT stack.

The following control parameters were used to calculate the depth dosedistributions for proton beams in the example presented herein: Thecutoff energy for particles was 20 keV, the Rayleigh effect wasconsidered, δ-ray production was turned on, continuous energy loss forparticles below cutoff energy levels sampled directly from the tables,Compton scattering was turned on, pair production with generation ofe⁻/e⁺ was considered, photoelectric effect was turned on, and positronannihilation with generation of photons was considered.

Results and Discussion: The PIC simulations show that the maximum protonenergy of the polyenergetic proton beam is a function of many variablesincluding the laser pulse intensity and duration, as well as the targetdensity and its thickness. The quantitative dependence of the maximumproton energy on laser/plasma target parameters can be found in Fourkalet al. The overall results of this study showed that the maximum protonenergy increases with decreasing thickness of the plasma target reachingthe plateau for the target thicknesses on the order of the hot electronDebye length (for a given laser intensity). In the same time, the protonenergy is a non-monotonous function of the laser pulse length, reachingthe maximum value for the laser-pulse length of the order of 50femtoseconds. Thus, depending on the simulation parameters, one canobtain a broad spectrum of energy distributions for the acceleratedprotons.

FIGS. 2( a) and 2(b) show the energy and angular distributions for theprotons accelerated by the laser pulse described above. For thelaser/plasma parameters chosen in the simulation, the maximum protonenergy reaches the value of 440 MeV, which is much higher than typicallyneeded for radiotherapy applications. To reduce the unwanted protons, aswell as to collimate them to a specific angular distribution, a primarycollimation device is provided. Its geometrical size and shape istypically tailored to the energy and angular proton distributions. Forexample, in one embodiment of the present invention there is provided a5 cm long tungsten collimator that absorbs the unwanted energycomponents. Because of its density and the requirement for thecompactness of the selection system, tungsten is a favorable choice forcollimation purposes. A suitable primary collimator opening provides a1×1 cm² field size defined at 100 cm SSD. Protons that move into anangle larger than this are typically blocked. With the magnetic fieldconfiguration shown in FIG. 1, for example, the solution to the equationof motion (1) with the initial conditions given by the proton phasespace spectra obtained from the PIC simulations, yields the protonspatial distributions N═N(y) at the plane x=40 cm, z=0 cm, as shown inFIG. 3. This shows that the magnetic field spreads the polyenergeticprotons into spatial regions according to their energy and angulardistributions. Their spatial distribution is such that the lower energyparticles are deflected at greater distances away from the central axis,and as the proton energy increases the spatial deflection decreases.Therefore, the contribution of both the magnetic field and the primarycollimator (with a specific collimator opening) creates such a spatialproton distribution that allows the energy selection or proton energyspectrum reformation, using an aperture. The geometric shape of anaperture typically determines the energy distribution of the therapeuticprotons.

As mentioned above, due to the presence of the angular spread, there istypically a spatial mixing of different energy protons. As a result ofthis mixing, the proton energy distribution in a given spatial locationis typically no longer monochromatic, but has a spread around its peak.FIG. 4 shows the proton energy distributions at different spatiallocations. These distributions were calculated by counting the number ofprotons in the given spatial location of width Δy=3 mm as a function ofenergy. This figure shows that the lower energy particles have a muchsmaller spread than the high energy particles. Without being bound to aparticular theory of operation, this result is apparently due to thehigher energy protons not being deflected as much in the magnetic fieldas are the lower energy particles. Because of the energy spread effect,the depth dose curves needed for the energy modulation calculationstypically are modified to include the effect of the energy spread in thecalculations, since mono-energetic protons are not typically for thedepth dose calculations. Using the GEANT3 Monte Carlo transport code thedose distributions for the proton energy spectra shown in FIG. 4 for a4×4 cm² field size was calculated. The results of the simulation areshown in FIG. 5. The presence of an energy spread in the proton spectraleads to the broadening of the dose distributions, which leads to a lesssharp falloff of the energy-modulated Bragg peak as compared to the caseof mono-energetic beams. See, e.g., T. Bortfeld. The broadening istypically most profound for the higher energy protons.

FIGS. 6( a) and 6(b) show the spatial distribution of protons N=N(y) atthe plane x-40 cm, z=0 cm for the magnetic field configuration shown inFIG. 1, using a primary collimator opening of 5×5 cm² defined at 100 cmSSD and the proton energy distributions N_(i)=N_(i)(E), where index idenotes the energy levels of the polyenergetic proton beams. ComparingFIG. 5, 6(a) and 6(b) to FIGS. 3 and 4 the spatial separation of protonsat larger openings is less effective leading to the higher order ofspatial mixing and the larger spread in the energy distributions. Theenergy spread as used herein is defined as the difference between themaximum and the minimum energy in the distribution. FIG. 7 shows theenergy spread as a function of a collimator opening for several protonenergy levels; the energy spread increases with increasing apertureopening and is more profound for higher energy particles.

As a result of the energy spread effect, the depth dose curves willtypically have less sharp falloff beyond the effective Bragg peak regionfor wider apertures as compared to the cases of narrower collimatoropenings. FIG. 8 shows the dose distributions for the proton energyspectra shown in FIG. 6( b), which corresponds to a primary collimatorof 5×5 cm² defined at 100 cm SSD, normalized to the incident protonfluence. Comparing FIG. 5 with FIG. 8 shows that desirable dosimetriccharacteristics from the laser accelerated protons are typicallyobtained for smaller primary collimator openings. Suitable primarycollimator openings are typically smaller than about 2000 cm², moretypically smaller than about 100 cm², and even more typically smallerthan about 1 cm², when defined at 100 cm SSD. Typically there is a lowerlimit on the size of the collimator opening, which is suitablydetermined by the field size, dose rate, or both, that the system canyield after beam collimation. The geometry of the collimator openingtypically influences the treatment time.

Once the depth dose distributions for polyenergetic proton beamlets aredetermined, a proton energy distribution that provides a homogeneousdose along the target's depth direction is calculated using the targetlocation and volume. In one embodiment, the following steps are carriedout to calculate the desired proton energy distribution:

1. The geometrical size of the target (in the depth direction)determines the proton energy range for radiating the target. Using thedepth dose distributions for a given energy range, the weights for theindividual polyenergetic beamlet are computed, with the assumption thatthe weight for the beamlet with the energy distribution, which gives theeffective Bragg peak at the distal edge of the target, is set to one.The weights W_(i)=W_(i)(E) are computed based on the requirement of theconstancy of the dose along the depth direction of the target.

2. Once the weights are known, the proton energy distribution N(E) forproviding a suitable dose along the target's depth dimension arecalculated by convolving the weights W_(i)(E) with the energydistributions N_(i)(E) of polyenergetic proton beamlets to give

$\begin{matrix}{{N(E)} = {\sum\limits_{i}{{W_{i}(E)}{N_{i}(E)}}}} & (4)\end{matrix}$where index i runs through energy levels of the polyenergetic protonbeamlets for radiating the area of interest (in depth direction). Asuitable energy modulation prescription for protons is provided by theformulation of the absorbed dose distribution for electrons introducedby Gustafsson, A., et al., in “A generalized pencil beam algorithm foroptimization of radiation therapy”, Med. Phys., 343–356 (1994), in whichthe incident particle differential energy fluence integrated over thesurface and solid angle corresponds to the energy distribution definedin Eq. (4). As an example, a hypothetical target with spatial dimensions4×4×5 cm³, located at depth lying between 9 cm and 14 cm is considered.The energy range of polyenergetic protons required to cover this targetis 110 MeV<E<152 MeV. Using both the depth dose distributions forpolyenergetic proton beamlets with the spread out energy spectradiscussed earlier and the condition of a constancy of the resultant dosealong the target's depth direction, the weights W_(i) for eachindividual beamlet, that are indicated in Table 1 are readily obtained.

TABLE 1 W₁₅₂ 1.00 W₁₄₉ 0.25 W₁₄₆ 0.15 W₁₄₃ 0.12 W₁₄₀ 0.10 W₁₃₇ 0.095W₁₃₄ 0.09 W₁₃₁ 0.085 W₁₂₈ 0.08 W₁₂₅ 0.07 W₁₂₂ 0.06 W₁₁₉ 0.05 W₁₁₆ 0.04W₁₁₃ 0.035 W₁₁₀ 0.03

Distribution of weights corresponding to protons with a differentcharacteristic energy: In one embodiment of the present invention, aprocedure for finding the weights is provided. This procedure ismathematically similar to minimizing the following functional

$\begin{matrix}{{{\Gamma(z)} = {{\sum\limits_{i}{W_{i}{D_{i}(z)}}} - D_{0}}},{{{for}\mspace{14mu} 9\mspace{14mu}{cm}} \leq z \leq {14\mspace{14mu}{cm}}}} & (5)\end{matrix}$where i denotes energy bins, D_(i) is the depth-dose distributioncorresponding to the ith polyenergetic energy bin and D₀ is a constantcorresponding to a specific dose level (typically larger than thedistant Bragg peak in view of the contribution from the adjacentdepth-dose distributions). The physical meaning of the weights aredescribed further. The absolute value of each individual weight iscorrelated to the physical method associated with the actual energymodulation process in the selection system. The design of the energymodulation system (i.e., the aperture) is achieved by either using anaperture whose geometric shape is correlated to the weights or by usinga slit, which can move along the y-axis in the region where the protonsare spread according to their energy levels, and the time spent in agiven region will be proportional to the value of the weight for thegiven energy. Convolving the weights of the Table (1) with the energydistributions for each individual beamlet according to equation (4), oneobtains the actual modulated energy distribution that will deliver theSOBP for the given target's depth dimension. This energy distributiondiffers from that calculated using monoenergetic proton beams (for whichthe weights themselves represent the actual energy distribution) becauseof the presence of particles with energy levels beyond the onesassociated with the weights, which typically arises from a consequenceof a finite primary collimator. The presence of these “extra particles”typically makes the dose distribution beyond the SOBP fall off lesssharply than that obtained using mono-energetic beams.

FIG. 9 shows the proton energy spectrum (a) and the corresponding dosedistribution (normalized to the incident proton fluence) (b) for atarget considered in the calculations. The resultant dose distributionshows the quick fall off of the dose beyond the distal edge of thetarget although not as dramatic as for an ideal case of convolvingmono-energetic protons shown also in FIG. 9( b). The entrance dose isstill significant compared to the dose to the target. In order to reducethe entrance dose, several proton beams coming from different directionsbut converging at the target could be used, so that the target receivesthe prescribed dose and the surrounding healthy tissue receives muchless dose. Therefore, the energy and intensity modulated proton therapyis expected to further improve target coverage and normal tissuesparing.

Dose Rate Determination: As mentioned earlier, it is important todetermine the absolute dose rate that the ion selection system canyield. This quantity is closely related to the absolute number ofaccelerated protons. From the PIC simulations it was determined that fora laser intensity of about I=1.9×10²² W/cm² and pulse length of about 14fs, the number of protons accelerated to energy levels higher than about9 MeV is about 4.4×10⁵ when the total number of protons used in PICsimulation is 1048576. Without being bound by a particular theory ofoperation, not all of the protons in the plasma slab are believed tointeract with the laser. Only those protons that are located in thelaser's propagation path typically experience the strongest interaction.

In simulation studies, the laser occupies an area of about ⅗ of thetotal size of the simulation box (in a direction perpendicular to thepropagation), which provides about 6.3×10⁵ protons (out of 1048576) thatwill “sample” the laser. This means that about 70% of the effectivenumber of protons are accelerated to energy levels higher than about 9MeV. On the other hand, the total number of protons in a plasma slabthat subtends the laser pulse can be estimated using the proton densityof the foil nf as well as the laser focal area S and the thickness ofthe foil d to give N=S×n_(f)×d≈2×10¹². Finally this gives aboutN=0.7*2×10¹²=1.4×10¹² protons that will be typically accelerated toenergy levels greater than about 9 MeV.

With the above in mind, the absolute dose delivered to the target isestimated in the following way. The polyenergetic beams needed to coverthe target in depth direction (9 cm≦z≦14 cm) will typically have anenergy range of about 110–152 MeV. The number of protons in the energyrange of about 147 MeV<E<157 MeV moving into the angle of 0.01 radian(approximately 2.6% of the total number of protons in the energy range147 MeV<E<157 MeV) is N=2.6×10⁸, which corresponds to Φ₀=2.6×10⁸ l/cm²(1×1 cm² field size) per laser pulse for the initial fluence of protonsat a distance of about 100 cm from the source.

FIG. 9( b) shows that the dose deposited by protons in the Monte Carlosimulations (normalized to the initial fluence) at depths 9 cm≦d≦14 cmis about D₀=1.6×10 ⁻⁹ Gy*cm². This gives D=D₀*Φ₀≈0.43 Gy per laser shot.Typical lasers operating in a 10 Hz repetition rate yield D≈256 Gy perminute for the pencil beam of 1×1 cm². The dose rate is typically notonly a function of laser-plasma parameters but also depends on thelocation and volume of the target. This leads to D≈64 Gy/min for thetarget located at depth z=25 cm (the distal edge of the target) withvolume of 1×1×5 cM³. While not being bound to any particular theory ofoperation, the reduction of the dose rate in this case is apparently dueto both the smaller number of protons in the energy range needed tocover the deeply seated target, as well as the less energy depositedwithin the target (the height of the Bragg peak gets smaller as theproton energy increases). The calculation presented above estimates theabsolute dose rate for 1×1 cm² pencil beam. More typically, thecross-section of the treatment volume is larger in area than 1×1 cm² andthe “effective” dose rate becomes smaller and comparable to that ofconventional linear accelerators. Larger targets can be effectivelytreated by scanning the high energy polyenergetic positive ion beam overthe target. In an alternative embodiment, treatment target volumeslarger than the cross section of the beam is irradiated by varying thefield size to cover the cross sectional depth at the field volume usingdifferent proton energy levels in individual beams. Multiple beamsvarying in energy, area, location and shape can be combined to conformto the targeted volume. For example, for the hypothetical targetconsidered in the energy-modulation calculations with spatial dimensionsof 4×4×5 cM³, the dose rate becomes D=256/16=16 Gy/min. The sameestimations would give D=4 Gy/min for a target located at depth z-25 cmand a volume of 4×4×5 cm³. The calculations presented above can also beused to estimate the treatment time needed for a given target. Assumingthe 2 Gy treatment regiment, the time needed to deliver this dose to atarget with a volume of 4×4×5 cm³ located at depth of 14 cm ist=2/16=0.125 minute. This is carried out using a laser-accelerated highenergy polyenergetic positive ion beam treatment center (200), such asthe one described in FIG. 17.

Referring to the laser-accelerated high energy polyenergetic positiveion beam treatment center (200) in FIG. 17, there is provided a mainlaser beam line (202) that is reflectively transported using a series ofbeam reflectors, e.g., mirrors (204, a–f), to a target and ion selectionsystem (100). The target and ion selection system (100) includes thetarget system for generating high energy polyenergetic ions and an ionseparation system, such as depicted schematically in FIG. 1 (withtarget) and 18 (without target). The proton beam exiting the target andion selection system includes therapeutically suitable high energypolyenergetic positive ions that are generated as described above. Asshown, the proton beam exiting the target and ion selection system aredirected in the direction parallel to the direction of the laser beamentering the target and ion selection system. The proton beam (206) isshown directed towards a couch (208), which locates the patient and thepatient's target. The mirrors (204 a–f) and target and ion selectionsystem (100) are capable of being rotated (here shown capable of beingrotated in the x-z plane, the z direction being perpendicular to the x-yplane) around the axis of the main laser beam line using a gantry.Typically, the final mirror (204, f) from which the laser beam isreflected into the target and ion selection system (100) is fixed to thetarget and ion selection system. The distance between the final mirror(204, f) and mirror (204, e) and ion selection system is shownadjustable along the y direction to permit scanning of the proton beam(206) along the y direction. The distance between mirror (e) and mirror(d) is shown adjustable along the x direction to permit scanning of theproton beam along the x direction. Suitable target and ion selectionsystems (100) are compact (i.e., less than about 100 to 200 kg in totalmass, and less than about 1 meter in dimension). The compactness of thetarget and ion selection systems permit their positioning withrobotically-controlled systems to provide rapid scanning of the protonbeam (206) up to about 10 cm/s.

One embodiment of the high energy polyenergetic positive ion beamradiation treatment centers of the present invention includes thecomponents as shown in FIG. 17, along with a suitable laser (such asdescribed with respect to FIG. 12 below) and a system for monitoring andcontrolling the therapeutically suitable high energy polyenergeticpositive ions. Suitable lasers are typically housed in a building, suchas in the same building as the positive ion beam treatment center, orpossibly in a nearby building connected by a conduit for containing thelaser beam. The main laser beam line (202) is typically transportedthrough the building within shielded vacuum conduit using a series ofmirrors (e.g., 204) to direct the laser beam (202) to the target and ionselection system (100). The target and ion selection system (100) istypically mounted on a gantry, which is placed in a treatment room. Inadditional embodiments of the present invention, the main laser beam(202) is split using a beam splitter into a plurality of laser beamsemanating from a single laser. Each of the laser beams emanating fromthe beam splitter is directed to an individual target and ion selectionsystem (100) for treating a patient. In this fashion, high energypolyenergetic positive ion radiation treatment centers are providedusing one laser source and a plurality of ion therapy systems to treat aplurality of patients. In certain embodiments of the high energypolyenergetic positive ion radiation treatment centers of the presentinvention, there are provided a plurality of treatment rooms, eachtreatment room having an individual target and ion selection system, alocation for a patient, and a proton beam monitoring and controllingsystem. A plurality of treatment rooms equipped this way enables agreater number of patients that can be treated with the investment ofone high power laser for providing therapeutically suitable high energypolyenergetic positive ions.

Laser-accelerated proton beams also typically generate neutrons, whichmay contaminate the ion beam. The energy modulation process leads to alarge portion of proton energy being deposited within the beam stoppersas well as the aperture and collimators. As described earlier,N=1.4×10¹² protons have energy levels higher than 9 MeV. In this regard,these protons can be accelerated by the laser, and only 0.02% of thetotal proton energy is allowed to go through the final collimator and bedeposited within the target. Proper shielding is typically provided toprevent the “waste” protons and unselected particles and theirdescendants from leaking out of the treatment unit. There is a finiteprobability that some of the contaminant particles may pass through thefinal (or secondary) collimating device (138) or leak out through theshielding. Determining the number of contaminant particles is typicallyconsidered in the shielding calculations.

Coulomb Expansion of Proton beam: Without being bound by a particulartheory of operation and referring to FIG. 1, it is believed that as theprotons go through the aperture (118), the subsequent recombiningmagnetic field configuration (112), and through the secondarycollimation device (138), the protons (134) form a non-neutral protonplasma with uncompensated charge, which typically tends to spread apartdue to a repulsive force arising from the Coulomb interaction among theprotons. This repulsive force typically introduces an extra divergenceto the proton beam in addition to the initial divergence. The initialdivergence is typically due to the angular spread of thelaser-accelerated protons, which is typically controlled by the geometryof the primary collimation device. The magnitude of the repulsive forcedepends on the proton density at the exit region. Both the theoreticaldescription as well as the particle in cell simulations can be used toestimate the rate at which the given distribution of protons willexpand. For simplicity, a spherically symmetrical distribution ofprotons with a given initial density and size is assumed to correspondto the size and density of the proton cloud at the exit region. Due tothe spherical symmetry of the problem considered, the subsequent timeevolution of the system typically maintains its symmetry. The equationof motion for the outer most protons, which can approximate the size ofa proton cloud, is, in the non-relativistic limit,

$\begin{matrix}{{m\frac{\mathbb{d}^{2}r}{\mathbb{d}t^{2}}} = {\frac{eQ}{4\;\pi\; ɛ_{0}}\frac{r}{r^{3}}}} & (6)\end{matrix}$where m is the proton mass and Q is the charge of the proton cloud. Itis convenient to introduce the dimensionless units τ=tω_(pi), r=RR₀,where R₀ is the initial radius of the proton cloud, ω_(pi)=√{square rootover (ne²/m_(p)ε₀)} is the proton plasma frequency and n is the initialproton density. In these units, the equation governing the evolution ofthe outer part of the proton cloud is,

$\begin{matrix}{\frac{\mathbb{d}^{2}R}{\mathbb{d}^{2}\tau} = \frac{R}{3R^{3}}} & (7)\end{matrix}$

The numerical solution to this equation with the initial conditions R=1,dR/dτ=0 when τ=0 is plotted in FIG. 10. To convert these results to thereal space-time variables, the value for the proton plasma frequencyω_(pi) is used, which in turn typically requires the knowledge of theinitial proton density in a cloud. The total number of protons in acloud can be estimated using the arguments presented earlier. Throughsuitable calculations, the number of protons accelerated to energylevels higher than about 9 MeV is determined to be about N≈1.4*10¹². Asmall fraction (≈0.03) of these protons typically pass through theinitial collimation device, giving N≈4*10¹⁰. In one embodiment of thepresent invention described in FIG. 1, where an exit point of theparticle selection system is at 70 cm away from the source, the volumethat the accelerated protons occupy is determined as the productV=ΔL_(x)ΔL_(y)Δ_(z), where ΔL_(x), ΔL_(y) and ΔL_(z) are the spatialdimensions of the proton cloud. For a 0.7×0.7 cm² field size, ΔL_(y)=0.7cm, ΔL_(z)=0.7 cm. ΔL_(x) can be found by calculating the spatialextent, at the exit point, between the fastest and the slowest particlesused for the therapeutic purposes (typically about 50 MeV<E<about 500MeV; and more typically about 80 MeV<E<about 250 MeV). For these energylevels, ΔL_(x)=L*(1−v_(s)/v_(f))≈25 cm. With that in mind, the averageproton density and the proton plasma frequency are n=N/V≈3.5×10¹⁰ cm⁻³,ω_(pi)≈6×10⁷ s⁻¹. Providing a patient location 1 meter (“m”) away fromthe secondary collimation device, the average time required for a protonbeam to reach a patient is t≈7*10⁻⁹ s, giving τ=ω_(pi)t=0.4. FIG. 10shows that at τ=0.4, a two to three percent increase in the size of theproton cloud is expected to arise primarily from the electrostaticrepulsion. FIG. 10 also shows the results of PIC simulations of thenon-neutral proton plasma dynamics with the initial conditionscorresponding to those used in this description. As shown here, there isa good agreement between the two approaches. The calculations shownabove represent an upper limit for the rate of proton divergence due tothe electrostatic repulsion. Typically, due to the energy modulationprocess, the total number of particles will be less than that used inthe calculations (since many of the initial protons will be discarded),thus a lower beam divergence rate due to the electrostatic repulsiontypically results.

In one embodiment of the present invention there is provided a protonselection system. The calculations provided herein show that ionselection systems of the present invention that utilize a magnetic fieldalong with a collimation device can generate proton beams with energyspectra suitable for radiation treatment. Due to the broad energy andangular distributions of the laser-accelerated protons, the ionselection system provides polyenergetic positive ion (e.g., proton)beams with energy distributions that have an energy spread in them,leading to broader dose distributions as compared to the case ofmonoenergetic protons. A design of this embodiment provides for acollimator opening of about 1×1 cm² defined at about 100 cm SSD, theenergy spread for about 80 MeV proton beam is about 9 MeV, and theenergy spread for about 250 MeV proton beam is about 50 MeV. In thissystem, as the primary aperture opening increases, the spread in protonenergy distributions increases as well. The calculated depth-dosedistributions for collimator openings of about 1×1 cm², about 5×5 cm²and about 10×10 cm² show the preference of using narrower apertures. Theaperture opening cannot be arbitrarily small, since it would decreasethe effective dose rate for larger targets. A collimator opening ofabout 1×1 cm² defined at about 100 cm SSD typically provides an adequatetreatment time as well as typically provides satisfactory depth-dosedistributions for energy-modulated proton beams.

The proton selection systems provided by the various embodiments of thepresent invention open up a way for generating small beamlets ofpolyenergetic protons that can be used for inverse treatment planning.Due to the dosimetric characteristics of protons, the energy andintensity modulated proton therapy can significantly improve theconformity of the dose to the treatment volume. In addition, healthytissues are spared using the methods of the present invention comparedto conventional treatments. Overall results suggest that the laseraccelerated protons together with the ion selection system for radiationtreatments will bring significant advances in the management of cancer.

Radiation therapy is one of the most effective treatment modalities forprostate cancer. In external beam radiation therapy, the use of protonbeams provides the possibility of superior dose conformity to thetreatment target and normal tissue sparing as a result of the Bragg peakeffect. FIG. 11 shows the energy deposition (or dose) as a function ofthe penetration depth for protons, photons (X-rays), electrons, andneutrons. While neutrons and photons (X-rays) show high entrance doseand slow attenuation with depth, monoenergetic protons have a very sharppeak of energy deposition as a function of the beam penetration justbefore propagation through tissue stops. As a consequence, it ispossible for almost all of the incident proton energy to be depositedwithin or very near the 3D tumor volume, avoiding radiation-inducedinjury to surrounding normal tissues. Protons have a higher linearenergy transfer component near the end of their range, and are expectedto be more effective biologically for radiotherapy of deep-seated tumorsthan conventional medical accelerator beams or cobalt-60 sources.

In spite of the dosimetric superiority characterized by the sharp Braggpeak, utilization of proton therapy has lagged far behind that ofphotons for prostate treatment. This is because the operating regime forproton accelerators is at least an order of magnitude higher in cost andcomplexity, which results in their being too expensive for widespreadclinical use compared to electron/photon medical accelerators.Conventional proton accelerators are cyclotrons and synchrotrons, ofwhich only two such medical facilities exist in the U.S., those ofMassachusetts General Hospital (MGH) (Jongen 1996, Flanz et al. 1998)and Loma Linda University Medical Center (LLUMC) (Cole 1991). Bothoccupy a very large space (entire floor or building). Although they aregrowing in number, only several such clinical facilities exist in theworld (Sisterson 1999). Despite a somewhat limited number of clinicalcases from these facilities, treatment records have shown encouragingresults particularly for well-localized radio resistant lesions(Sisterson 1989, 1996; Austin-Seymour et al., Duggan and Morgan 1997;Seddon et al. 1990; Kjellberg 1986). The degree of clinicaleffectiveness for a wide variety of malignancies has not been quantifieddue to limited treatment experience with this beam modality. Thissituation will be greatly improved by the availability of a compact,flexible, and cost-effective proton therapy system, as provided by thepresent invention. The present invention enables the widespread use ofthis superior beam modality and therefore bring significant advances inthe management of cancers, such as brain, lung, breast and prostatecancers.

In one embodiment of the present invention there is provided a compact,flexible and cost-effective proton therapy system. This embodimentrelies on three technological breakthroughs: (1) laser-acceleration ofhigh-energy polyenergetic protons, (2) compact system design for ionselection and beam collimation, and (3) treatment optimization softwareto utilize laser-accelerated proton beams. As described above,laser-proton sources have been developed to accelerate protons usinglaser-induced plasmas. U.S. patent application Ser. No. 09/757,150 filedJan. 8, 2001, Pub. No. U.S. 2002/0090194 A1, Pub. Date Jul. 11, 2002,“Laser Driven Ion Accelerator”, discloses a system and method ofaccelerating ions in an accelerator using such a laser light sourcesystem, the details of which are incorporated by reference herein intheir entirety. Such laser-proton sources are compact for the reasonthat the accelerating gradient induced by the laser is far greater, andthe beam emittance is far smaller, than current radio-frequency andmagnet technology based cyclotrons and synchrotrons (Umstadter et al.1996).

One embodiment of the present invention provides an ion-selection systemin which a magnetic field is used to spread the laser-acceleratedprotons spatially based on their energy levels and emitting angles, andapertures of different shapes are used to select protons within atherapeutic window of energy and angle. Such a compact device eliminatesthe need for the massive beam transportation and collimating equipmentthat is common in conventional proton therapy systems. The laser-protonsource and the ion selection and collimating device of the presentinvention are typically installed on a treatment gantry (such asprovided by a conventional clinical accelerator) to form a compacttreatment unit, which can be installed in a conventional radiotherapytreatment room.

A treatment optimization algorithm is also provided to utilize the smallpencil beams of protons generated with ion selection systems of thepresent invention to obtain conformal dose distributions for cancertherapy, such as for prostate treatment. In various embodiments of thepresent invention there are provided optimal target configurations forlaser-proton acceleration and methods for ion selection and beamcollimation. In this embodiment of the present invention, dosedistributions of laser-accelerated protons for cancer treatment aretypically determined by dose calculation of proton beamlets,optimization of beamlet weights and delivery of beamlets using efficientscan sequence. Commercial software is available for carrying outintensity modulation of photon beams for targeting. Such software can beadapted for use with laser-accelerated proton beams by the followingsteps: calculating dose needed; optimizing the weights of the beam; anddetermining the sequence of the therapeutically suitable high energypolyenergetic positive ion beams. As a specific example, the treatmentof prostate cancer is carried out by selecting beam incident anglesbased on the target volume and its relationship with the criticalstructures (rectum, bladder and femurs), preparing positive ion beamswith different shapes, sizes and/or energies, optimizing the weights ofindividual beamlets, generating a scan sequence based on the beamweights, and verifying the final dose distribution by Monte Carlocalculations or by measuring with a suitable monitoring device.

Laser acceleration was first suggested in 1979 for electrons (Tajima andDawson 1979) and rapid progress in laser-electron acceleration began inthe 1990's after chirped pulse amplification (CPA) was invented(Strickland et al. 1985) and convenient high fluence solid-state lasermaterials such as Ti:sapphire were discovered and developed. The firstexperiment that has observed protons generated with energy levels muchbeyond several MeV is based on the Petawatt Laser at the LawrenceLivermore National Laboratory (LLNL) (Key et al. 1999, Snavely et al.2000). Until then there had been several experiments that observedprotons of energy levels up to 1 or 2 MeV, which were considered to be‘standard’ (Maximchuck et al. 2000). Another experiment at theRutherford-Appleton Laboratory in the U.K. has been reported recentlywith proton energy levels of up to 30 MeV (Clark et al. 2000). ThePetawatt Laser is a specially modified arm of large NOVA Laser at LLNL.The pulse is shortened by the CPA technique (Strickland et al. 1985)into several hundred fs (femtosecond, fs=10⁻¹⁵ sec), but it is notultrashort (i.e. in the range of tens of fs). In the latest PetawattLaser experiments, high-energy protons of 58 MeV were observed (Key etal. 1999, Snavely et al. 2000). A surprisingly large fraction of laserenergy (of the order of 10%) was converted into proton energy in theseexperiments. Without being bound by a particular theory of operation,the electrostatic field generated by electrons driven by the laser isgenerally considered to be the main initiator (Wilks et al. 1999).Hydrogen atoms and thus protons, which are quickly generated fromionization of hydrogen, are typically accelerated from the back surfaceof the metal due to the electronic space charge to high energy levels.There are several relevant theoretical and computational studies ofproton acceleration at high laser intensities (Rau et al. 1998; Bulanovet al. 1999; Wilks et al. 1999; Ueshima et al. 1999, Fourkal et al.2002a).

Experimental investigations on laser-proton acceleration using a shortpulsed CPA intense Ti:sapphire laser (JanUSP) have been carried out.This technology is different from that of the Petawatt Laser (based on aglass laser). The short-pulsed Ti:sapphire laser can be much morecompact and have higher repetition than the glass laser. This isparticularly useful for radiotherapy applications as multiple shorts aretypically needed for one treatment. The JanUSP laser system is shown inFIG. 12. A continuous train of 800 nm sub-100 fs pulses is emitted froma commercial mode locked oscillator pumped by 8 Watts of 530 nm light.The time-frequency transform limited oscillator output is stretched in afolded diffraction grating pulse stretcher to approximately 250 ps. Thestretched 4 nJ pulse is then amplified in a regenerative amplifier to 8mJ and then to 220 mJ in a 5 pass amplifier in a bow-tie configuration.Isolation from amplified spontaneous emission and pre-pulse leakage fromthe regenerative amplifier is provided by three stages of glan polarizerPockel cell pulse slicers. The portion of the laser operates at 10 Hzand 90 mJ energy, allowing both rapid setup and timing of diagnostics atintensities up to 10¹⁹ W/cm². Two additional stages of amplification arepumped by a frequency doubled Nd:Silicate glass amplifier. These finalamplifiers raise the stretched beam energy to greater than 21 J. Avacuum compressor employing two 40 cm diameter gratings is used forpulse recompression to 80 fs. The 200 TW compressed pulse is routed invacuum to the target chamber, where it is focused onto the target by a15 cm diameter F/2 off-axis parabola to provide focal intensities ontarget of >2×10²¹ W/cm². The Gaussian focal spot is approximately 2 μmin diameter. Because of its high focal intensity, the JanUSP laser is asuitable laser that is coupled to a targeting system for generating highenergy polyenergetic ion beams in accordance with the invention.

A facility for a laser-accelerated ion therapy system can be designedusing previous neutron treatment suites in existing cancer treatmentfacilities, which provide adequate space and shielding. A typical laseruseful in the ion therapy system has a similar construction as theJanUSP laser. The laser pulse repetition rate is typically designed at arate of from 1–100 Hz, but typically is about 2 to 50 Hz, and mosttypically about 10 Hz. Laser intensity is typically in the range of fromabout 10¹⁷ W/cm² to about 10²⁴ W/cm², more typically in the range offrom about 10¹⁹ W/cm² to about 10²³ W/cm², and even more typically inthe range of from about 10²⁰ W/cm² to about 10²² W/cm², and mosttypically about 10²¹ W/cm², which is commercially available.

It has been found that the target configuration plays an important rolein laser-proton acceleration. At an intensity of 10²¹ W/cm², recenttheoretical and computational results (Tajima 1999; Ueshima et al. 1999)show that under favorable conditions protons can be accelerated up toabout 400 MeV (Table 2). It was found (Tajima 1999) that the innovationof the target and judicious choice of laser and target parameters canyield a large number of protons with energy levels>100 MeV. Depending onthe details of the target preparation and geometry, as well as the pulselength and shape, the average and maximum energy levels of protons (andother ions) vary. In Case 3, with the most sophisticated target, theaverage proton energy is in excess of 100 MeV and the maximum is 400MeV. The energy converted into ions amounts to 14% of the incoming laserenergy. This efficiency is consistent with the Petawatt Laser, whereabout 10% conversion efficiency into protons was observed althoughparameters and preparations differed from Case 3.

TABLE 2 Particle-in-cell (PIC) Results (Ueshima et al. 1999) on protonand electron acceleration by laser irradiation on three thin targets. Alaser intensity of 10²¹ W/cm²on the target surface is applied. Case 1Case 2 Case 3 Energy conversion 50% 24% 31% Ion  4%  8% 14% Electron 48%16% 17% Peak energy H⁺ 200 MeV 400 MeV 400 MeV Peak energy Al¹⁰⁺  1 GeV 2 GeV  2 GeV Peak energy electron  25 MeV  15 MeV  20 MeV Averageenergy H⁺  58 MeV  95 MeV 115 MeV Average energy Al¹⁰⁺ 130 MeV 500 MeV500 MeV

Without being bound to a particular theory of operation, a high laserintensity in the range of from about 10¹⁷ W/cm² to about 10²⁴ W/cm² isbelieved to be an important parameter in the generation and accelerationof positive ions to energy levels suitable for radiation therapy. Another important parameter is the design of suitable targets thatgenerate polyenergetic protons. Various suitable targets for generatinghigh energy polyenergetic positive ions are known. Suitable targets havebeen designed using various materials, dimensions, and geometry. Laserirradiation fashion, e.g., intensity and spot size, is also known toinfluence the generation of positive ions. According to preliminary PICsimulations of the optimized laser target interaction (Ueshima et al.1999; Tajima 1999, Fourkal et al. 2002a), the charge separation distanceof a few microns with the electrostatic field on the order of 100 GeV/mmis expected to develop upon the irradiation of high Z materials(electron density of about 10²⁴/cm³). With this field over thisdistance, protons can be accelerated to energy levels greater than 100MeV. With proper geometry and dimensions of the target, the averageproton energy levels may be increased by several times over a simpletarget. U.S. patent application Ser. No. 09/757,150 filed Jan. 8, 2001,Pub. No. U.S. 2002/0090194 A1, Pub. Date Jul. 11, 2002, “Laser DrivenIon Accelerator”, is incorporated by reference herein for thedisclosures pertaining to target construction used in a laser-protonaccelerator systems. Such targets are suitably used in variousembodiments of the present invention.

In Table 2, Case 3, with a particular target shape, an average protonenergy greater than 100 MeV and the maximum energy at 400 MeV areprovided. Various target configurations are readily tested for higherenergy proton generation.

Based on these laser specifications, particle-in-cell (PIC) simulationshave also been performed to investigate the effect of target shape,material and laser pulse length on the energy of laser-acceleratedprotons (Fourkal et al. 2002a). These results show that using a laserintensity of 10²¹ W/cm² and a pulse length of 50 fs, protons can beaccelerated to 310 MeV. FIG. 13 shows the angular distributions of theseprotons and the maximum proton energy as a function of the laser pulselength for the same laser intensity. The raw proton beams from alaser-driven proton accelerator have a broad energy spectrum andvariable beam profiles for different energy levels; they typicallycannot be used directly for therapeutic applications. One solution tothis problem is to design a compact ion selection and collimation devicein order to deliver small pencil beams (beamlets) of protons withdesired energy spectra to cover the treatment depth range, as describedearlier above and further below.

As shown in FIG. 14, 1 cm×1 cm beamlet depth dose curves are providedfor different polyenergetic protons, described above. By combining thedepth dose curves of different spectra, a spread out Bragg peak (SOBP)is achieved that covers the treatment target in the depth direction(FIG. 15). This process is termed herein, “energy modulation”. Althoughthe spectrum-based (polyenergetic) SOBP is not as clean as themonoenergetic SOBP, the weights of individual proton beamlets can bevaried through an optimization routine to conform the dose distributionto the target laterally. As used herein, this process is termed“intensity modulation”, which is commonly used for photon beamtreatments. The estimated dose rate for the laser proton beams shown inFIGS. 14 and 15 is 1–20 Gy per minute for field sizes from 1 cm×1 cm to20 cm×20 cm. Intensity-modulated radiation therapy (IMRT) using photonbeams typically can deliver more conformal dose distributions to theprostate target (and the associated nodes) compared to conventional 4–6photon field treatments. Modulation of the dose distribution of photonbeams in the depth direction is essentially impossible, however, this isnot the case with proton beams (Verhey and Munzenrider 1982).Accordingly, energy- and intensity-modulated proton therapy (EIMPT)further improves target coverage and normal tissue sparing for radiationtreatments, such as for the treatment of prostate cancer. Thecombination of a compact ion selection and collimation device and anassociated treatment optimization algorithm typically makes EIMPTpossible using laser-accelerated proton beams. Without being bound to aparticular theory of operation, the polyenergetic nature of a laserproton beam makes it ideal for EIMPT since it is convenient for bothenergy modulation (using a spectrum) and intensity modulation (throughbeam scanning).

To demonstrate the superiority of EIMPT for prostate treatment, dosedistributions of prostate plans using different treatment modalitieswere compared (Ma et al. 2001a, Shahine et al. 2001). FIG. 16 shows dosevolume histograms (DVH) of the target and the rectum for a prostatetreatment. The proton isodose distribution is also shown. The photonIMRT plan was derived from a commercial treatment optimization system,CORVUS (NOMOS Corp., Sewickley, Pa.) using eight 15 MeV photon beams.The gantry angles were 45, 85, 115, 145, 215, 245, 275, and 315 degrees.The 8-field conventional proton plan included energy modulation but didnot have intensity modulation. The proton beams were incident at thesame gantry angles as the photon IMRT plan. The 8-field EIMPT includedboth energy modulation and intensity modulation with the same gantryangles. The 4-field conventional proton plan was derived using only 45,115, 245, and 315 degrees ports. This shows that target coverage can besignificantly improved using both energy- and intensity-modulation in aproton treatment. The rectum dose is much lower with the 8 field EIMPTcompared to other beam modalities. The 8-field conventional proton planis better than the 4-field proton plan and the latter is better than the8-field photon IMRT plan in terms of the rectum dose. The results of Maet al. 2001a are consistent with the findings of Cella et al. (2001),who compared 5-field intensity-modulated proton beams with 5-field IMRT(the Memorial Sloan-Kettering Cancer Center technique, Burman et al.1997), 2-field conventional protons (the LLUMC technique, Slater et al.1998), and the conventional 6-field photon treatment for prostate. EIMPTplans are consistently superior to conventional treatments and IMRTplans in target coverage and normal tissue sparing (lower doses torectum, bladder and femoral heads).

The results of Ma et al. 2001a described above assumed ideal energyselection and beam collimation for the proton beamlets. The actualbeamlet dose distributions of realistic proton spectra generated by theion radiation system of the present invention will typically not be thesame as the ideal dose distributions used in the preliminarycalculations of Ma et al. 2001 a, which also used a 2D patient geometryto generate these plans.

The present inventor has demonstrated that different beamlet dosedistributions can be combined through beamlet optimization to obtainideal dose distributions. In one embodiment of the present invention,PIC simulations are performed to derive optimal target configurationsand laser parameters and then use the simulated proton beam data todesign an efficient ion selection and beam collimation device. Thesimulated proton phase space data is used for the Monte Carlosimulations to obtain accurate dose distributions using the protonbeamlets from the proton therapy unit to achieve optimal target coverageand normal tissue sparing.

Through energy- and intensity-modulation, high-energy protons generatedby a laser-accelerated proton source are developed into an effectivemodality for radiation therapy. The positive ion therapy systems of thepresent invention are comparable to conventional photon clinicalaccelerators both in size and in cost. Therefore, the widespread use ofthis compact, flexible and low-cost proton source will result insignificant benefits for cancer patients.

Methods

System Design: As described above, the raw proton beams accelerated bylaser induced plasmas typically cannot be used directly for radiotherapytreatment. An important component of a laser proton radiotherapy systemis a compact ion selection and beam collimation device, which is coupledto a compact laser-proton source to deliver small pencil beams ofprotons of different energy levels and intensities. In one embodiment ofthe present invention there is provided an overall design of alaser-proton therapy system, which includes system structure and layout,mechanisms of the major components and research strategies for theexperiment work (Ma 2000). FIG. 17 shows a schematic diagram of oneembodiment of a laser-accelerated positive ion beam treatment center(e.g., laser-proton therapy unit, the laser not shown). The laser andthe treatment unit are typically placed on the same suspension bench toensure laser beam alignment (negligible energy loss due to the smalldistance). This also keeps the whole system compact. The target assemblyand the ion selection device are placed on a rotating gantry and thelaser beam is transported to the final focusing mirror 204(f) through aseries of mirrors 204(a–e). The distances between mirrors 204(d) and204(e) and mirrors 204(e) and 204(f) are adjusted to scan the protonbeam along x- and y-axis, respectively, which generates a parallelscanned beam. An alternative method is to swing the target and ionselection device about the laser beam axis defined by mirrors 204(d) and204(e) and that defined by 204(e) and 204(f), respectively, to achieve ascan pattern. This generates a divergent scan beam. The treatment couchis adjusted to perform coplanar and noncoplanar, isocentric and SSD(source-to-surface distance) treatments.

PIC study of proton acceleration: PIC simulations of targetconfigurations and laser parameters are carried out for optimizing laserproton acceleration. The PIC simulation method computes the motions of acollection of charged particles (e.g., ions) interacting with each otherand with externally applied fields. Charged plasma species are modeledas individual macroparticles (each macroparticle represents a largenumber of real particles). Since the spatial resolution is limited bythe size of the particle, the spatial grid (cell) is introduced acrossthe simulation box. The size of the grid is approximately equal to thesize of the macroparticle. The charge densities as well as the electriccurrents are calculated at each grid position by assigning particles tothe grid according to their position employing a weighting scheme. Oncethe charge density and the current density at the grid positions areknown, the electric and magnetic fields at the same grid points arecalculated using Poisson's and Maxwell's equations. These equations aretypically solved using Fast Fourier Transforms (FFT). Fields at theparticle positions are subsequently determined using an inverseweighting scheme in which the fields at the grid points are interpolatedto the points of particle locations to yield the fields at particlelocations. Particles are then moved via Newton's equations, using aleap-frog finite differencing method (positions and fields arecalculated at integer time-steps, velocities at half time-steps). Thisprocedure is repeated to give the time evolution of the system. Atwo-dimensional, electromagnetic relativistic PIC code is typically usedfor carrying out these optimization experiments. At each time step, thecoordinates and momenta of the particles and electromagnetic field arecalculated for the given initial and boundary conditions. All thevariables to be calculated are functions of time and two spatialcoordinates x and y. Different laser parameters and target geometry aresimulated. Further details of our PIC simulations are described furtherherein and in Fourkal et al., 2002a.

PIC simulations are performed using the codes developed by Tajima(1989). These one to two-and-one-half dimensional, first-principle, fulldynamics physics tools are particularly effective for ultrafast intenselaser matter interaction. Those skilled in the art are experienced withhigh field science analyses (for example, Tajima et al. 2000) and withPIC simulations in plasma physics (Fourkal et al. 2002a). These skillscan be applied to simulate previous experiments and the experimentalsetups currently used to confirm the experimental laser-protonacceleration results. The experimental situations are analyzed and theconfigurations and parameters are optimized to guide furtherexperiments. Suitable targets used are typically simple freestandingplanar foils and composite planar foils of plastic and other materials.Dense gas targets are also suitable targets. PIC simulations of thesetarget configurations using different laser intensities, focal spotsizes and pulse lengths can be performed of the ion radiation facilityof the present invention. An optimal set of laser parameters is foundusing these simulations that can produce protons of energy levels up toat least 250 MeV with small angular distribution and high dose rate.These PIC simulation results are used for further analytical studies onthe ion selection and beam collimation system.

Characterization of laser-accelerated proton beams: Accuratedetermination of the characteristics of all the particle components in alaser-accelerated proton beam is particularly important. This knowledgeassists the design and operation of the ion selection and beamcollimation system. The energy, angular and spatial distributions oflaser-accelerated protons are evaluated from the PIC simulations. Beamcharacterization studies are carried out for source modeling and beamcommissioning for further dosimetric studies. Several Monte Carlo codeshave been installed, expanded and extensively used for radiation therapydose calculation including EGS4 (Nelson et al. 1985), PENELOPE (Salvatet al. 1996), PTRAN (Berger 1993), and GEANT (Goosens et al. 1993). Thecodes typically run on a PC network consisting of 16 Pentium III (866MHz) microprocessors. Magnetic field distributions are simulated usingcommercial software, which is suitable for 3-dimensional fieldsimulation and the results are compared with measurements of an ionradiation system of the present invention. Radiation transport in amagnetic field has been extensively simulated for electron beams (Ma etal. 2001b, Lee and Ma 2000). Software is implemented and verified forprotons to obtain proton energy, angular and spatial distributions atthe exit window of the laser-proton device. The geometry of an ionradiation system of the present invention is used in the simulations.The characteristics of the anticipated beams are studied to evaluatetheir advantages and disadvantages for radiation oncology application.

Analytical study of ion selection and beam collimation: To use theproton beams for treatment, one typically removes the contaminantphotons, neutrons and electrons from the beam using any of a variety ofbeam stopping and shielding materials. In preferred embodiments of theion selection systems of the present invention, low-field magnets areused to separate the four major radiation components. As shownschematically in FIG. 18, several 3 Tesla magnetic fields (220, 222,224) are used to deflect protons a small angle. A photon beam stopper(228) is placed on the beam axis (230). Suitable beam stoppers (228,234) are used to remove unwanted low- and high-energy protons. Thematching magnetic field setup in this embodiment assists the recombiningof the selected protons, and the final beam is collimated by the primaryand secondary collimators 242 and 240, respectively. The opening of thecollimator is typically small (about 0.5 cm×0.5 cm), and the collimatorsare typically greater than about 10 cm in total thickness. Scatteredprotons from the beam stoppers 228, 234 and the protons missing theopening of the aperture are not transmitted through the collimatoropening. As the bremsstrahlung photons and neutrons are also forwarddirected, a 1–2 cm wide, 10 cm thick tungsten stopper typically stopsall the direct particles and the scattered particles are terminated bythe shielding materials (not shown). Electrons typically are deflecteddownward by the magnetic field (220) and absorbed by an electronstopper. FIG. 19( a) shows the proton energy and angular distributionsbefore and after ion selection. Lower energy protons (140) typicallyhave larger angular spread compared to higher energy protons (142). InFIG. 19( b), lower energy protons (140) they typically spread over alarger area (244) spatially after going through the magnets compared tothe spatial spread (246) of higher energy protons. An aperture (238)typically is used to select the desired energy components. FIG. 19( c)shows the energy spectrum of raw protons (solid line) and that of theresulting selected protons (dashed line). FIG. 19( d) shows the depthdose curve of raw protons solid line) and that of the resulting selectedprotons (dashed line). A secondary monitor chamber (240) (“SMC” in FIG.18) measures the intensity of each energy component. A primary monitorchamber (242) (“PMC” in FIG. 18) is also provided. Various ways ofmonitoring ion beams and control systems are disclosed in U.S. patentapplication Ser. No. 09/757,150 filed Jan. 8, 2001, Pub. No. U.S.2002/0090194 A1, Pub. Date Jul. 11, 2002, “Laser Driven IonAccelerator”, the portion of which pertaining to monitoring ion beamsand control systems is incorporated by reference herein. A suitablelaser-proton beam, as selected by the ion selection system (100) of thepresent invention, typically has an energy spectrum suitable for adesired treatment depth range (uniform dose over that range). By using aplurality of beams, a conformal and uniform dose coverage in the beamdirection is achieved for essentially any target shape and depth.

The design parameters for the ion selection and collimating system usingthe experimental setup described above can be optimized by those skilledin the art. Because the proton beams are very small in cross-section,suitable magnetic field (“B-field”) sources for providing high magneticfields within a small space are used. Suitable magnets for providingsuch magnetic fields are readily available to those skilled in the art.The ion selection system of the present invention does not requirestrict B-field spatial distribution, for example, the fields may have aslow gradient or a fast gradient. Likewise, the opposing B-fields may bematched or mismatched. One skilled in the art can perform theoreticaloptimization studies on different magnets to determine various compactgeometries. A suitable compact geometry is illustrated in FIG. 18, whichprovides dimensions of less than 50 cm in length and less than 40 cm indiameter. The properties of the primary beam for treatment and theleakage through the collimating system together with other contaminantparticles can be investigated using a numerical simulation program forfurther treatment planning dose calculations. Criteria for protonspectra and beamlet dose distributions are determined based on theminimum requirements for beam penumbra laterally and in the depthdirection for treatment optimization. The results are used to guidefurther optimization work on collimator design and proton energyselection and modulation studies. Source models for the proton beams arealso investigated so that for patient simulation, the phase-spaceinformation can be reconstructed from the source models rather thanusing large phase-space data files (inefficient for simulation and largedisk space, Ma 1998, Ma et al. 1997) or simulating the laser protondevice every time. Beam commissioning procedures are also established byone skilled in the art for validating the source model parameters andthe beam reconstruction accuracy.

FIG. 20 illustrates one set of design principles of the presentinvention of the ion selection mechanism. Since different laser-protonshave different angular distributions (three energy levels are shown inFIG. 20( a)), a collimator (e.g. 108, FIG. 1) is typically used (i.e.,positioned at the distance along beam axis 0 cm in FIG. 18) to definethe field size. When the initial collimator (108) has a square opening,and the polyenergetic collimated protons of different energy levels havepassed through the magnet fields, the collimated protons will reachdifferent transverse locations (250) (as shown at the distance 30 cm inFIG. 18). FIG. 20 (a and b) shows the square fields of 50, 150 and 250MeV protons, which are well separated spatially. The transverse plane isreferred to as “the energy space (plane)” as different proton energylevels typically occupy different transverse locations. Because of thefinite size of the initial collimator there typically is some overlap ofproton energy levels, which typically depends on the size of the initialcollimator, the magnetic field strength and the distance from the energyplane to the initial collimator. For selecting the desired energy ofthis embodiment, a second collimator is typically used, which istypically positioned at the corresponding transverse location. As shownin FIG. 20( b), a square aperture (248) (on the right hand side) is usedto select either the 50, 150 or the 250 MeV field. A differentialtransmission chamber (the secondary monitor chamber, SMC in FIG. 18) isused to measure the intensity of each energy component. Multiple laserpulses are typically provided to produce a combination of protons toprovide a desired spectrum. The desired proton energy spectrum is usedto produce a therapeutically high energy polyenergetic positive ionbeam, which provides uniform dose distributions over a desired depthrange.

Another embodiment of the ion selection system of the present inventionis to use variable aperture sizes at the energy space (plane) to selectboth an energy and the total number of protons of that energy(intensity) simultaneously. This embodiment typically requires fewerlaser pulses to achieve a desired proton spectrum compared to thepreceding embodiment. This variable aperture size embodiment preferablyuses an elongated aperture at the energy space with variable widths atdifferent transverse (energy) locations. Without being bound by aparticular theory of operation, this design allows for energy andintensity selection simultaneously from the same laser pulse. Thisappears to be a highly efficient way to use a polyenergetic laser-protonbeam to achieve a uniform dose over a depth range for radiation therapy.A variable energy aperture size typically uses a subsequent differentialmagnetic system to recombine the fields of different proton energylevels to a similar field size.

In certain embodiments, a secondary collimation device (138) (FIG. 1) istypically provided to define the final field size and shape of thepositive ions that form the therapeutically suitable high energypolyenergetic positive ion beam. Small shaped beams (e.g., squares,circles, rectangles, and combinations thereof) are provided in tomodulate the intensity of individual beamlets so that a conformal dosedistribution to the target volume can be achieved. Since the individualproton beams can have variable energy spectra for providing a uniformdose distribution over the depth range of the target volume, EIMPT canbe used to produce a more uniform proton dose distribution in the targetthan photon IMRT (Lomax 1999, Ma et al. 2001).

Another method of modulating the spatially separated high energypolyenergetic positive ion beam is to deliver EIMRT using a plurality ofindividual narrow energy polyenergetic proton beams at a time with arelatively large field that covers at least a portion of thecross-section of the target volume at the corresponding depth (i.e., thedepth of the Bragg Peak). In this embodiment, there is provided amodulatable secondary collimation device that is capable of modulatingthe spatially separated beam. The modulatable secondary collimationdevice may have a variable shape, which can be realized using anaperture, as described earlier, such as a multileaf collimator (MLC). Anumber of laser pulses are typically provided using this embodiment totreat a target volume. While the aperture that modulates the energylevels typically moves in the transverse direction to select a desiredenergy spectrum to cover the depth range of at least a portion of theentire target volume, the modulatable secondary collimation devices(e.g., the MLC) are capable of changing the field shape of therecombined beam to enclose at least a portion of the cross-section ofthe target volume at the corresponding depths.

The methods described herein for the ion selection systems (100) of thepresent invention may suitably be performed using the devices andinstrumentalities described herein. Because the proton beams aretypically small in cross-section, it is possible to establish a highmagnetic field within a small space. Certain embodiments of the presentinvention do not require strict B-field spatial distribution, rather,the magnetic fields may have a slow gradient, they may be spatiallyoverlapping, or both. Suitable embodiments of the present invention willinclude at least two magnetic field sources that have matching,opposite, B-fields. For example, the ion selection system geometryprovided in FIG. 18, which is less than 50 cm in length and less than 40cm in diameter, includes a first magnetic field source (220) of 3.0 Tinto the page, a second magnet field source (224) of 3.0 T into thepage, and a third magnetic field source (222) of 3.0 T out of the page.The geometry may be further reduced in the beam direction by usinghigher magnetic fields, smaller photon beam stoppers, or both.

Improvement of Monte Carlo dose calculation tools: Dose calculationtools for EIMPT are also provided in accordance with the invention. Dosecalculation is performed in treatment optimization for laser acceleratedproton beam therapy because the dose distributions of small protonbeamlets are significantly affected by the beam size and heterogeneouspatient anatomy. Patient dose calculations are estimated using theGEANT3 system. The code is designed as a general purpose Monte Carlosimulation. The dose distributions shown in FIG. 16 (a–d) took about 100hours of CPU time on a Pentium III 450 MHz PC. Much faster computersthat are currently available should be able to reduce this computationtime by at least about one or two orders of magnitude. For acceleratingdose calculation, a fast proton dose calculation algorithm has beendeveloped based on conventional photon and electron Monte Carlo dosecalculation algorithms (Ma et al. 1999a–b, 2000ab, Deng et al. 2000ab,Jiang et al. 2000a, 2001, Li et al. 2000, 2001). Various variancereduction techniques have been implemented in the code to speed up theMonte Carlo simulation. These include “deterministic sampling” and“particle track repeating” (Ma et al. 2000b, Li et al. 2000), which arevery efficient for charged particle simulations. The implementation ofthis fast Monte Carlo code is tested using the GEANT3 code. The sourcemodels are also implemented to reconstruct the phase-space parameters(energy, charge, direction and location) for the proton pencil beamsemerging from the laser proton therapy device during a Monte Carlo dosecalculation. Suitable software is available (Moyers et al 1992, Ma etal. 1999b) that can be adapted for use in treating patients withlaser-accelerated polyenergetic positive ions. Such software firstconverts the patient CT data into a simulation phantom consisting ofair, tissue, lung and bone. Based on the contours of the target volumeand critical structures, the software computes the dose distributionsfor all the beamlets of different spectra, incident angles (e.g., gantryangles specified by the planner), and incident locations (e.g., within atreatment port/field). The final dose array for all the beamlets isprovided to the treatment optimization algorithm, as described furtherbelow.

Improvement of treatment optimization tools: In certain embodiments,improved treatment optimization tools for EIMPT are also provided. Atreatment optimization algorithm has been developed based on typicalpolyenergetic proton beams generated from a typical laser protonaccelerator and actual patient anatomy. Commonly used “inverse-planning”techniques include computer simulated annealing (Webb 1990, 1994),iterative methods (Holmes and Mackie 1994a, Xing and Chen 1996),filtered back projection and direct Fourier transformation (Brahme 1988,Holmes and Mackie 1994b). Considering the calculation time and thepossible complexity with proton beams, the iterative optimizationapproach (based on a gradient search) is suitably adopted. This is basedon iterative optimization algorithms for photon and electron energy- andintensity-modulation (Pawlicki et al. 1999; Jiang 1998, Ma et al. 2000b,Jiang et al. 2000b). Improved algorithms for energy- andintensity-modulated proton beams are tested. Further improvements of thealgorithm is carried out in view of the special features of therealistic proton beams. The “optimizer” performs the following tasks:(1) takes the beamlet dose distributions from the dose calculationalgorithm (see above), (2) adjusts the beamlet weights (intensities) toproduce the best possible treatment plan based on the target/criticalstructure dose prescriptions, and (3) outputs the intensity maps(beamlet weighting factors) for all the beam ports and gantry angles forbeam delivery sequence studies.

Treatment plan comparison: The present invention has been evaluated forthe treatment modality for prostate cancer. Comparisons are made oftreatment plans generated by EIMPT using laser-accelerated proton beamswith those generated by existing beam modalities such as conventionalphoton and proton beams and photon IMRT. A group of 20 clinical casesfor prostate alone, prostate+seminal vesicles, and prostate+seminalvesicles+lymph nodes have been performed using EIMPT under the sameconditions as for conventional radiotherapy treatments usingconventional photons and protons and photon IMRT. The treatment plansare compared with those using a commercial RTP system for conventionalphoton beams with 4 or 6 photon fields (the FOCUS system) and acommercial treatment optimization system for IMRT with 5–9 intensitymodulated photon fields (the CORVUS system). These cases are alsoplanned using the proton treatment planning module in the FOCUS system,for conventional proton treatments with 2–6 fields.

The plans are evaluated using isodose distributions, DVHs, TCP, NTCP andother biological indices with emphasis on target coverage, target dosehomogeneity and normal tissue sparing. The same objective (penalty)functions are used for both proton EIMPT and photon IMRT, under similarconditions. The “goodness” of a treatment plan is judged based on theappearance of the isodose distributions and on DVH, TCP, NTCP and otherbiological indices. A significantly improved plan is considered topossess one or more of the following: (a) more uniform (5–10%) dosewithin the target volume, much less (moderate vs. high or low vs.moderate) dose to the immediately adjacent normal structures, (b) asignificantly reduced exit/scatter dose (by a factor of two or more) toremote organs, and (d) an unambiguously improved dose distribution.Furthermore, a physician typically makes a clinical judgment as towhether a particular plan would be used and provide reasons justifyingthis decision.

Production of Radioisotopes. The present invention also provides methodsof producing radioisotopes using the laser-accelerated high energypolyenergetic ion beams provided herein. The production of 2-deoxy-2-¹⁸Ffluoro-D-glucose (“[¹⁸F]FDG”) is carried out by proton bombardment ofthe chemical precursors leading to the radioisotopes. These processesuse proton beams generated using traditional cyclotron and synchrotronsources. For example, J. Medema, et al.[http://www.kvi.n1/˜agorcalc/ecpm31/abstracts/medema2.html] havereported on the production of [¹⁸F] Fluoride and [¹⁸F] FDG by firstpreparing [¹⁸F] fluoride via the ¹⁸O(p, n) [¹⁸F] nuclear reaction in ¹⁸Oenriched water, and producing the [¹⁸F]FDG by recovering the[¹⁸F]fluoride via the resin method and the cryptate drying process. Thepresent invention provides high energy polyenergetic ion beams suitablefor use in this process of preparing radioisotopes. Thus, the process ofproducing radioisotopes includes the steps of forming a high energypolyenergetic proton beam as described herein to provide an appropriateparticle, target and beam current. A target precursor is filled with H₂¹⁸O. The high energy polyenergetic proton beam irradiates the targetprecursor until a preselected integrated beam current or time isreached. The target pressure is typically monitored by a pressuretransducer. When the integrated beam current or the time is reached the[¹⁸F]fluoride is used for chemically synthesizing [¹⁸F] FDG. The finalproduct is isotonic, colorless, sterile, and pyrogen free and issuitable for clinical use.

Various alternate embodiments of the present invention are furtherdepicted in FIGS. 21–44, in which the ion tracks are illustrated toprovide a general position and orientation of the ions. For example,FIGS. 21, 23 (schematic cross sections) and 22 (perspective) depicts anembodiment of an ion selection system (100) composed of a collimationdevice (408) capable of collimating a laser-accelerated high energypolyenergetic positive ion beam, the laser-accelerated high energypolyenergetic ion beam having a plurality of high energy polyenergeticpositive ions; a first magnetic field source (magnet 202) capable ofspatially separating the high energy polyenergetic positive ionsaccording to their energy levels; an aperture (418) capable ofmodulating the spatially separated high energy polyenergetic positiveions; and a second magnetic field source (magnet 412) capable ofrecombining the modulated high energy polyenergetic positive ions.

FIG. 24 depicts a schematic of an embodiment of an ion selection systemsimilar to that provided in FIG. 21 that further includes a thirdmagnetic field source (magnet 420), the third magnetic field sourcecapable of bending the trajectories (428) of the spatially separatedhigh energy polyenergetic positive ions towards the aperture (418).

FIG. 25 depicts a schematic of an embodiment of an ion selection systemsimilar to that provided in FIG. 24 that shows the aperture (418) beingplaced inside the magnetic field of the third magnetic field source(magnet 420).

FIG. 26 depicts a schematic of an embodiment of an ion selection systemsimilar to that provided in FIG. 24 that shows the aperture (418) beingplaced outside of the magnetic field of the third magnetic field source(magnet 420), where the third magnetic field source is separated intotwo portions.

FIG. 27 depicts a schematic of an embodiment of an ion selection systemin which the magnetic field of the third magnetic field source (magnet420) is capable of bending the trajectories (428) of the modulated highenergy polyenergetic positive ions towards the second magnetic fieldsource (magnet 412).

FIG. 28 depicts a schematic of an embodiment of an ion selection systemin which the second magnetic field source (magnet 412) is capable ofbending the trajectories (428) of the modulated high energypolyenergetic positive ions towards a direction that is not parallel tothe direction of the laser-accelerated high energy polyenergetic ionbeam.

FIG. 29 depicts a schematic of an embodiment of an ion selection systemin which the second magnetic field source (magnet 412) is capable ofbending the trajectories (428) of the modulated high energypolyenergetic positive ions towards a direction that is parallel to thedirection of the laser-accelerated high energy polyenergetic ion beam.

FIG. 30 depicts a schematic of an embodiment of an ion selection systemthat further shows a secondary collimation device (430) capable offluidically communicating a portion of the recombined high energypolyenergetic positive ions therethrough.

FIG. 31 depicts an embodiment of an ion selection system that shows asecondary collimation device (430) that is capable of modulating thebeam shape of the recombined high energy polyenergetic positive ions.

FIG. 32 depicts details of a rotatable wheel (440) with an aperture(418) having a plurality of openings (442, 444), each of the openingscapable of fluidically communicating high energy polyenergetic positiveions therethrough.

FIG. 33 depicts details of an aperture that is a multileaf collimator(408) having openings (444, 442) that are capable of passing low energyions, high energy ions, respectively, or a combination thereof.

FIG. 34 depicts how an ion selection system in accordance with theinvention manipulates ion beams. This figure depicts the forming of alaser-accelerated high energy polyenergetic ion beam including aplurality of high energy polyenergetic positive ions (110), the highenergy polyenergetic positive ions (110) characterized as having adistribution of energy levels. The collimating of the laser-acceleratedion beam (110) is performed using a collimation device (collimator 408),and the positive ions (140, 142) are spatially separated according totheir energy levels using a first magnetic field (magnet 402). Thespatially separated high energy polyenergetic positive ions aremodulated using an energy selection aperture (418) and the modulatedhigh energy polyenergetic positive ions are recombined (428) using asecond magnetic field (magnet 412). In this embodiment, a portion of thepositive ions are transmitted through the aperture, e.g., having energylevels in the range of from about 50 MeV to about 250 MeV, and otherportions are blocked by the energy selection aperture (418).

FIG. 35 depicts the bending of the trajectories of the positive ions(140, 142) in a direction away from the beam axis of thelaser-accelerated high energy polyenergetic ion beam (110) using thefirst magnetic field (magnet 402).

FIG. 36 depicts the bending of the trajectories of the spatiallyseparated positive ions (140, 142) in a direction towards aperture (444)using the third magnetic field (magnet 420).

FIGS. 37 and 38 depict the spatially separated high energy positive ionsbeing modulated by energy level (low energy (140) and high energy (142),respectively) using a location-controllable opening in aperture (442,444).

FIG. 39 depicts an embodiment of an ion selection system in which thethird magnetic field (magnet 420) is capable of bending the selectedpositive ions towards the second magnetic field (magnet 412), as in FIG.28.

FIG. 40 depicts an embodiment of an ion selection system in which thehigh energy polyenergetic positive ions are spatially separated overdistances up to about 50 cm.

FIG. 41 depicts an embodiment of an ion therapy system that includes alaser-targeting system, the laser-targeting comprising a laser and atargeting system (104) capable of producing a high energy polyenergeticion beam (110), the high energy polyenergetic ion beam including highenergy polyenergetic positive ions having energy levels of at leastabout 50 MeV. The high energy polyenergetic positive ions are spatiallyseparated (428) based on energy level (140, 142), and an ion selectionsystem capable of producing a therapeutically suitable high energypolyenergetic positive ion beam from a portion of the high energypolyenergetic positive ions is provided. Also provided is a differentialchamber (448) and an integration chamber (446). Positive ions ofdifferent energies will typically pass through different parts of thedifferential chamber (448) that measures the differences in energies ofthe ions, which monitors the energy of the selected ions. Typically, thedifferential chamber (448) does not control the energy selectionaperture, The integration chamber is provided to generate a signal thatis analyzed (e.g., by a computer or suitable data processor, not shown)to determine the position of the aperture (418) and the apertureopenings.

FIGS. 42( a–d) depicts perspective diagrams of a variety oflaser-accelerated high energy polyenergetic positive ion beam treatmentcenters (200), that each suitably include at least one of the iontherapy systems depicted in FIGS. 21–41 and a location for securing apatient (i.e., a couch, 208). For example, FIG. 42( a) depicts asuitable treatment center of the type described above with respect toFIG. 17 in which the laser beam (202) is reflectively transported to thetarget assembly (100) using a plurality of mirrors (204). FIG. 42( b)depicts a suitable treatment center that includes an optical monitoringand control system (450) for the laser beam (202). FIG. 42( c) depicts asuitable treatment center in which at least one beam splitter or mirror(452) is provided to split the laser beam (202) into split or reflectedlaser beams 454 to each of at least two target assemblies (100) or toreflect the laser beam to one of the target assemblies (100). Depictedis a suitable treatment center that shows the laser-targeting systemhaving two target assemblies and two ion selection systems each capableof individually producing a therapeutically suitable high energypolyenergetic positive ion beam from each of the individual high energypolyenergetic positive ion beams. An individual polyenergetic ion beammonitoring and control system is also provided for each of thetherapeutically suitable high energy polyenergetic positive ion beams.This embodiment depicts a mirror (452) that is capable of beingpositioned in and out of the main laser beam to direct the beam to oneof the ion therapy systems. Alternatively, a beam splitter can be usedwhen a sufficiently powerful laser beam is provided so that split beamscan be used simultaneously by two or more ion therapy systems. Forproviding patient privacy, typical ion therapy centers having two ormore ion therapy systems will have an individual treatment room for eachof the ion therapy systems. In such embodiments, the laser beam sourceis suitably located in a separate room or building. FIG. 42( d) depictsan embodiment of the treatment center that further includes an opticalmonitoring system (450). In this embodiment, the optical monitoringsystem (450) permits the operator to know, and control, which of the iontherapy systems is being activated.

FIG. 43 is a flow-chart (500) of a method of treating a patient inaccordance with the invention. This method includes the steps (502–508)of identifying the position of a targeted region in a patient,determining the treatment strategy of the targeted region, the treatmentstrategy comprising determining the dose distributions of a plurality oftherapeutically suitable high energy polyenergetic positive ion beamsfor irradiating the targeted region (e.g., determining the energydistribution, intensity and direction of a plurality of therapeuticallysuitable high energy polyenergetic positive ion beams); forming theplurality of therapeutically suitable high energy polyenergetic positiveion beams from a plurality of high energy polyenergetic positive ions,the high energy polyenergetic positive ions being spatially separatedbased on energy level; and delivering the plurality of therapeuticallysuitable polyenergetic positive ion beams to the targeted regionaccording to the treatment strategy.

Thus, methods and systems providing high energy polyenergetic positiveion radiation therapy have been provided. While the present inventionhas been described in connection with the exemplary embodiments of thevarious figures, it is to be understood that other similar embodimentsmay be used or modifications and additions may be made to the describedembodiment for performing the same function of the present inventionwithout deviating therefrom. For example, one skilled in the art willrecognize that the present invention as described in the presentapplication may apply to any configuration of magnets, apertures andcollimators that selects positive ions based on energy from a source oflaser-accelerated high energy polyenergetic positive ions. Therefore,the present invention should not be limited to any single embodiment,but rather should be construed in breadth and scope in accordance withthe appended claims.

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1. An ion selection system, comprising: a collimation device capable ofcollimating a laser-accelerated high energy polyenergetic ion beam, saidlaser-accelerated high energy polyenergetic ion beam comprising aplurality of high energy polyenergetic positive ions; a first magneticfield source capable of spatially separating said high energypolyenergetic positive ions according to their energy levels; anaperture capable of modulating the spatially separated high energypolyenergetic positive ions; and a second magnetic field source capableof recombining the modulated high energy polyenergetic positive ions. 2.The ion selection system of claim 1, wherein the modulated high energypolyenergetic positive ions have energy levels in the range of fromabout 50 MeV to about 250 MeV.
 3. The ion selection system of claim 1,wherein said first magnetic field source is capable of bending thetrajectories of the high energy polyenergetic positive ions away from abeam axis of said laser-accelerated polyenergetic ion beam.
 4. The ionselection system of claim 3, further comprising a third magnetic fieldsource, said third magnetic field source capable of bending thetrajectories of the spatially separated high energy polyenergeticpositive ions towards the aperture.
 5. The ion selection system of claim4, wherein the aperture is placed outside of the magnetic field of saidthird magnetic field.
 6. The ion selection system of claim 4, whereinthe magnetic field of said third magnetic field source is capable ofbending the trajectories of the modulated high energy polyenergeticpositive ions towards the second magnetic field source.
 7. The ionselection system of claim 6, wherein the second magnetic field source iscapable of bending the trajectories of the modulated high energypolyenergetic positive ions towards a direction parallel to thedirection of the laser-accelerated high energy polyenergetic ion beam.8. The ion selection system of claim 1, further comprising a secondarycollimation device capable of fluidically communicating a portion of therecombined high energy polyenergetic positive ions therethrough.
 9. Theion selection system of claim 8, wherein said secondary collimationdevice is capable of modulating the beam shape of the recombined highenergy polyenergetic positive ions.
 10. The ion selection system ofclaim 1, wherein said aperture comprises a plurality of openings, eachof the openings capable of fluidically communicating high energypolyenergetic positive ions therethrough.
 11. The ion selection systemof claim 10, wherein the aperture is a multileaf collimator.
 12. Amethod of forming a high energy polyenergetic positive ion beam,comprising: forming a laser-accelerated high energy polyenergetic ionbeam comprising a plurality of high energy polyenergetic positive ions,said high energy polyenergetic positive ions characterized as having adistribution of energy levels; collimating said laser-accelerated ionbeam using a collimation device; spatially separating said high energypositive ions according to their energy levels using a first magneticfield; modulating the spatially separated high energy polyenergeticpositive ions using an aperture; and recombining the modulated highenergy polyenergetic positive ions using a second magnetic field. 13.The method according to claim 12, wherein the step of modulating thespatially separated high energy polyenergetic positive ions gives riseto a portion of the positive ions being transmitted through theaperture, said portion of the positive ions having energy levels in therange of from about 50 MeV to about 250 MeV.
 14. The method according toclaim 12, wherein said trajectories of the high energy polyenergeticpositive ions are bent away from a beam axis of said laser-acceleratedhigh energy polyenergetic ion beam using said first magnetic field. 15.The method according to claim 14, wherein the trajectories of thespatially separated high energy polyenergetic positive ions are furtherbent towards the aperture using a third magnetic field.
 16. The methodaccording to claim 15, wherein the spatially separated high energypositive ions are modulated by energy level using a plurality ofcontrollable openings in said aperture.
 17. The method according toclaim 15, wherein the third magnetic field further bends saidtrajectories towards the second magnetic field.
 18. The method accordingto claim 17, wherein the second magnetic field bends said trajectoriestowards a direction parallel to the direction of a laser-acceleratedhigh energy polyenergetic ion beam.
 19. The method according to claim12, wherein a portion of the recombined high energy polyenergeticpositive ions is fluidically communicated through a secondarycollimation device.
 20. The method according to claim 12, wherein aplurality of high energy polyenergetic positive ion beamlets arefluidically communicated through a plurality of controllable openings insaid aperture to modulate the spatially separated high energy positiveions.
 21. The method according to claim 12, wherein the high energypolyenergetic positive ions are spatially separated over distances up toabout 50 cm according to an energy distribution of the high energypolyenergetic positive ions, said distances being measuredperpendicularly to a beam axis of said laser-accelerated ion beamentering the first magnetic field.
 22. The method of claim 12, furthercomprising irradiating a radioisotope precursor with the recombinedspatially separated high energy polyenergetic positive ions.
 23. Alaser-accelerated high energy polyenergetic positive ion therapy system,comprising: a laser-targeting system, said laser-targeting comprising alaser and a targeting system capable of producing a high energypolyenergetic ion beam, said high energy polyenergetic ion beamcomprising high energy polyenergetic positive ions having energy levelsof at least about 50 MeV, the high energy polyenergetic positive ionsbeing spatially separated based on energy level; an ion selection systemcapable of producing a therapeutically suitable high energypolyenergetic positive ion beam from a portion of said high energypolyenergetic positive ions; and an ion beam monitoring and controlsystem.
 24. The laser-accelerated high energy polyenergetic positive iontherapy system of claim 23, wherein the ion selection system comprises:a collimation device capable of collimating said laser-accelerated highenergy polyenergetic ion beam; a first magnetic field source capable ofspatially separating said high energy polyenergetic positive ionsaccording to their energy levels; an aperture capable of modulating thespatially separated high energy polyenergetic positive ions; and asecond magnetic field source capable of recombining the modulated highenergy polyenergetic positive ions.
 25. The laser-accelerated highenergy polyenergetic positive ion therapy system of claim 24, whereinthe modulated high energy polyenergetic positive ions are characterizedas having energy levels in the range of from about 50 MeV to about 250MeV.
 26. The laser-accelerated high energy polyenergetic positive iontherapy system of claim 24, wherein said first magnetic field sourceprovides a first magnetic field, said first magnetic field capable ofbending the trajectories of the high energy polyenergetic positive ions,said bending being in a direction away from a beam axis of saidlaser-accelerated high energy polyenergetic ion beam.
 27. Thelaser-accelerated high energy polyenergetic positive ion therapy systemof claim 26, wherein the ion selection system further comprises a thirdmagnetic field source, said third magnetic field source capable ofbending the trajectories of the spatially separated high energypolyenergetic positive ions towards the aperture.
 28. Thelaser-accelerated high energy polyenergetic positive ion therapy systemof claim 27, wherein the aperture is placed outside of the magneticfield of said third magnetic field.
 29. The laser-accelerated highenergy polyenergetic positive ion therapy system of claim 27, whereinthe magnetic field of said third magnetic field source is capable ofbending the trajectories of said portion of the spatially separated highenergy polyenergetic positive ions towards the second magnetic fieldsource.
 30. The laser-accelerated high energy polyenergetic positive iontherapy system of claim 29, wherein the second magnetic field source iscapable of bending the trajectories of said portion of the spatiallyseparated high energy polyenergetic positive ions towards a directionparallel to a beam axis of the laser-accelerated high energypolyenergetic ion beam.
 31. The laser-accelerated high energypolyenergetic positive ion therapy system of claim 24, furthercomprising a secondary collimation device capable of fluidicallycommunicating a portion of the recombined high energy polyenergeticpositive ions therethrough.
 32. The laser-accelerated high energypolyenergetic positive ion therapy system of claim 31, wherein thesecondary collimation device is capable of modulating a beam shape ofthe recombined high energy polyenergetic positive ions.
 33. Thelaser-accelerated high energy polyenergetic positive ion therapy systemof claim 24, wherein said aperture comprises a plurality of openings,each of the openings capable of fluidically communicating ion beamletstherethrough.
 34. A method of treating a patient with alaser-accelerated high energy polyenergetic positive ion therapy system,comprising: identifying the position of a targeted region in a patient;determining the treatment strategy of the targeted region, saidtreatment strategy comprising determining the dose distributions of aplurality of therapeutically suitable high energy polyenergetic positiveion beams for irradiating the targeted region; forming said plurality oftherapeutically suitable high energy polyenergetic positive ion beamsfrom a plurality of high energy polyenergetic positive ions, the highenergy polyenergetic positive ions being spatially separated based onenergy level; and delivering the plurality of therapeutically suitablepolyenergetic positive ion beams to the targeted region according to thetreatment strategy.
 35. The method of treating a patient according toclaim 34, wherein determining the dose distributions comprisesdetermining the energy distribution, intensity and direction of aplurality of therapeutically suitable high energy polyenergetic positiveion beams.
 36. The method of treating a patient according to claim 34,wherein said therapeutically suitable polyenergetic positive ion beamsare prepared by: forming a laser-accelerated high energy polyenergeticion beam comprising high energy polyenergetic positive ions; collimatingsaid laser-accelerated high energy polyenergetic ion beam using at leastone collimation device; spatially separating said high energypolyenergetic positive ions according to their energy levels using afirst magnetic field; modulating the spatially separated high energypolyenergetic positive ions using an aperture; and recombining themodulated high energy polyenergetic positive ions using a secondmagnetic field.
 37. The method of treating a patient according to claim36, wherein the modulated high energy polyenergetic positive ions haveenergy levels in the range of from about 50 MeV to about 250 MeV. 38.The method of treating a patient according to claim 36, wherein thetrajectories of the high energy polyenergetic positive ions are bentaway from a beam axis of said laser-accelerated high energypolyenergetic ion beam using said first magnetic field.
 39. The methodof treating a patient according to claim 38, wherein the trajectories ofthe spatially separated high energy polyenergetic positive ions are benttowards the aperture using a third magnetic field.
 40. The method oftreating a patient according to claim 39, wherein the spatiallyseparated high energy polyenergetic positive ions are modulated byenergy level using a plurality of controllable openings in saidaperture.
 41. The method of treating a patient according to claim 40,wherein the trajectories of the modulated high energy polyenergeticpositive ions are further bent towards the second magnetic field usingsaid third magnetic field.
 42. The method of treating a patientaccording to claim 41, wherein the trajectories of the modulated highenergy polyenergetic positive ions are bent towards a direction parallelto the direction of a beam axis of the laser-accelerated high energypolyenergetic ion beam using said second magnetic field.
 43. The methodof treating a patient according to claim 36, wherein a portion of therecombined high energy polyenergetic positive ions are fluidicallycommunicated through a secondary collimation device.
 44. The method oftreating a patient according to claim 43, wherein the beam shape of therecombined high energy polyenergetic positive ions is modulated by thesecondary collimation device.
 45. A laser-accelerated high energypolyenergetic positive ion beam treatment center, comprising: a locationfor securing a patient; and a laser-accelerated high energypolyenergetic positive ion therapy system capable of delivering atherapeutically suitable high energy polyenergetic positive ion beam toa patient at said location, the ion therapy system comprising: alaser-targeting system, said laser-targeting system comprising a laserand a target assembly capable of producing a high energy polyenergeticion beam, said high energy polyenergetic ion beam comprising high energypolyenergetic positive ions having energy levels of at least about 50MeV; an ion selection system capable of producing a therapeuticallysuitable high energy polyenergetic positive ion beam using said highenergy polyenergetic positive ions, the high energy polyenergeticpositive ions being spatially separated based on energy level; and amonitoring and control system for said therapeutically suitable highenergy polyenergetic positive ion beam.
 46. The laser-accelerated highenergy polyenergetic positive ion beam treatment center of claim 45,wherein the ion selection system comprises: a collimation device capableof collimating said high energy polyenergetic ion beam; a first magneticfield source capable of spatially separating said high energypolyenergetic positive ions according to their energy levels; anaperture capable of modulating the spatially separated high energypolyenergetic positive ions; and a second magnetic field source capableof recombining the modulated high energy polyenergetic positive ionsinto said therapeutically suitable high energy polyenergetic positiveion beam.
 47. The laser-accelerated high energy polyenergetic positiveion beam treatment center of claim 46, wherein the modulated high energypolyenergetic positive ions are characterized as having energy levels inthe range of from about 50 MeV to about 250 MeV.
 48. Thelaser-accelerated high energy polyenergetic positive ion beam treatmentcenter of claim 46, wherein said first magnetic field source is capableof bending the trajectories of the high energy polyenergetic positiveions away from a beam axis of said laser-accelerated polyenergetic ionbeam entering the first magnetic field.
 49. The laser-accelerated highenergy polyenergetic positive ion beam treatment center of claim 48,wherein the ion selection system further comprises a third magneticfield source capable of bending the trajectories of the spatiallyseparated high energy polyenergetic positive ions towards the aperture.50. The laser-accelerated high energy polyenergetic positive ion beamtreatment center of claim 49, wherein the aperture is placed outside ofthe magnetic field of said third magnetic field.
 51. Thelaser-accelerated high energy polyenergetic positive ion beam treatmentcenter of claim 49, wherein the magnetic field of said third magneticfield source is capable of bending the trajectories of the modulatedhigh energy positive ions towards the second magnetic field source. 52.The laser-accelerated high energy polyenergetic positive ion beamtreatment center of claim 51, wherein the second magnetic field sourceis capable of bending the trajectories of the modulated high energypolyenergetic positive ions towards a direction parallel to a beam axisof the laser-accelerated high energy polyenergetic ion beam.
 53. Thelaser-accelerated high energy polyenergetic positive ion beam treatmentcenter of claim 48, further comprising a secondary collimation devicecapable of fluidically communicating a portion of the recombined highenergy polyenergetic positive ions therethrough.
 54. Thelaser-accelerated high energy polyenergetic positive ion beam treatmentcenter of claim 46, wherein said aperture comprises a plurality ofopenings, each of the openings capable of fluidically communicating ionbeamlets therethrough.
 55. The laser-accelerated high energypolyenergetic positive ion beam treatment center of claim 45, whereinthe target assembly and the ion selection system are placed on arotating gantry.
 56. The laser-accelerated high energy polyenergeticpositive ion beam treatment center of claim 45, wherein a laser beam ofsaid laser is reflectively transported to the target assembly using aplurality of mirrors.
 57. The laser-accelerated high energypolyenergetic positive ion beam treatment center of claim 56, whereinthe ion selection system is robotically mounted to give permit scanningof the therapeutically suitable high energy polyenergetic positive ionbeam.
 58. The laser-accelerated high energy polyenergetic positive ionbeam treatment center of claim 56, further comprising at least one beamsplitter to split the laser beam to each of at least two targetassemblies.
 59. The laser-accelerated high energy polyenergetic positiveion beam treatment center of claim 45, wherein the laser-targetingsystem comprises a plurality of target assemblies, each of said targetassemblies capable of producing a high energy polyenergetic positive ionbeam, said high energy polyenergetic positive ion beam comprising highenergy polyenergetic positive ions comprising energy levels of at leastabout 50 MeV; a plurality of ion selection systems each capable ofindividually producing a therapeutically suitable high energypolyenergetic positive ion beam from each of said individual high energypolyenergetic positive ion beams; and an individual polyenergetic ionbeam monitoring and control system for each of said therapeuticallysuitable high energy polyenergetic positive ion beams.
 60. A method ofproducing radioisotopes, comprising: forming a high energy polyenergeticpositive ion beam, comprising: forming a laser-accelerated high energypolyenergetic ion beam comprising a plurality of high energypolyenergetic positive ions, said high energy positive ionscharacterized as having an energy distribution; collimating saidlaser-accelerated ion beam using at least one collimation device;spatially separating said high energy polyenergetic positive ionsaccording to energy using a first magnetic field; modulating thespatially separated high energy polyenergetic positive ions using anaperture; and recombining the spatially separated high energypolyenergetic positive ions using a second magnetic field; andirradiating a radioisotope precursor with the recombined spatiallyseparated high energy polyenergetic positive ions.